加载中

    logo
    Multiple-treatments meta-analysis of chemotherapy and targeted therapies in advanced breast cancer. Mauri Davide,Polyzos Nikolaos P,Salanti Georgia,Pavlidis Nicholas,Ioannidis John P A Journal of the National Cancer Institute BACKGROUND:Many systemic nonhormonal regimens have been evaluated across several hundreds of randomized trials in advanced breast cancer. We aimed to quantify the relative merits of these regimens in prolonging survival. METHODS:We performed a systematic review of all trials that compared different regimens involving chemotherapy and/or targeted therapy in advanced breast cancer (1973-2007). Regimens were categorized a priori into different treatment types. We performed multiple-treatments meta-analysis and calculated hazard ratios for each treatment category relative to monotherapy with old agents (ie, regimens not including anthracyclines, anthracenediones, vinorelbine, gemcitabine, capecitabine, taxanes, marimastat, thalidomide, trastuzumab, lapatinib, or bevacizumab). RESULTS:We identified 370 eligible randomized trials (54,189 patients), of which 172 (31,552 patients) compared different types of treatment. Survival data from 148 comparisons pertaining to 128 of the 172 trials (26,031 patients, 22 different types of treatment) were available for inclusion in the multiple-treatments meta-analysis. Compared with single-agent chemotherapy with old nonanthracycline drugs, anthracycline regimens achieved 22%-33% relative risk reductions in mortality (ie, hazard ratio [HR] for standard-dose anthracycline-based combination: 0.67, 95% credibility interval [CrI] 0.57-0.78). Several newer regimens achieved further benefits (eg, HR [95% CrI] 0.67 [0.55-0.81] for single-drug taxane, 0.64 [0.53-0.78] for combination of anthracyclines with taxane, 0.49 [0.37-0.67] for taxane-based combination with capecitabine or gemcitabine), and similar benefits were seen with several regimens including molecular targeted treatments. Most regimens had very similar efficacy profiles (<5% difference in HR) as first- and subsequent-line therapies. CONCLUSIONS:Stepwise improvements in efficacy of chemotherapy and targeted treatments cumulatively have achieved major improvements in the survival of patients with advanced breast cancer. Many options that can be used in first and subsequent lines of therapy have comparable efficacy profiles. 10.1093/jnci/djn414
    Phase I study of weekly vinorelbine in combination with weekly paclitaxel in adult patients with advanced refractory cancer. Cohen R B,Mueller S C,Haden K,de Souza P Cancer investigation Vinorelbine and paclitaxel are highly active antineoplastic agents. Preclinical data indicate a potential for antitumor synergy for a number of common tumor types when they are combined. We investigated a novel weekly schedule of both agents. Eighteen patients with advanced cancer were entered onto this phase I trial. Vinorelbine and paclitaxel were given weekly in combination for 6 consecutive weeks, followed by a 2-week break. Sequential cohorts of patients were treated at two dose levels: vinorelbine 22.5 mg/m2 followed by paclitaxel 40 mg/m2 and vinorelbine 22.5 mg/m2 followed by paclitaxel 60 mg/m2. Ten patients completed at least one 8-week course of therapy. Neutropenic myelosuppression was dose limiting at level II. Neurotoxicity was not dose limiting. Objective responses were seen in patients with esophageal, lung, and breast cancer and suggest that this is an active regimen worthy of further investigation in selected diseases. Phase II trials of this regimen are in progress.
    Phase II trial of weekly i.v. vinorelbine as a single agent in first-line advanced breast cancer chemotherapy. The Latin-American experience. Bruno S,Puerto V L,Mickiewicz E,Hegg R,Texeira L C,Gaitan L,Martinez L,Fernandez O,Otero J,Kesselring G American journal of clinical oncology This study investigated the therapeutic effect of single-agent i.v. weekly Navelbine (vinorelbine), a semisynthetic vinca alkaloid, in women who had received no prior treatment for locally advanced or metastatic breast cancer. Of 68 patients entered into the study, 63 were adequate inclusions, assessable for toxicity and response by WHO criteria; the 5 patients who were not evaluated were excluded from analysis because they were found not to meet the eligibility criteria of the study. Navelbine was given as a weekly 30 mg/m2 short i.v. (20 minutes) infusion; treatment was continued until disease progression. The overall response rate was 44% (complete response 8%, partial response 36%). The response rate according to target was lymph nodes, 62.9%; liver, 50.0%; lung, 50.0%; skin, 37.5%; and primary tumor, 30.8%. The median duration of response was 17.9 weeks (range: 7-52 weeks). The median time to treatment failure was 12.9 weeks, and the median survival was 50.3 weeks. The 63 eligible patients received 501 cycles. The mean dose intensity was 76%. At least one episode of WHO grade 3/4 granulocytopenia was seen in 46% of the patients (13.6% of cycles). Significant nausea/vomiting was seen in only 5% of patients corresponding to 1% of cycles. Only 5% of patients developed WHO grade 3-4 constipation and grade 3 peripheral neuropathy was observed in 1.6% of patients. Alopecia was rare (6.3% of patients), and other side effects were uncommon. This study confirms that Navelbine has major single-agent antitumor activity as frontline therapy in advanced breast cancer. Given its excellent tolerance profile and low morbidity, it should be recommended for inclusion in first-line combination chemotherapy regimens.
    Intravenous vinorelbine as first-line and second-line therapy in advanced breast cancer. Weber B L,Vogel C,Jones S,Harvey H,Hutchins L,Bigley J,Hohneker J Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:We evaluated single-agent intravenous (IV) vinorelbine as first- and second-line treatment for advanced breast cancer (ABC) in patients who were not resistant to anthracyclines. Objective tumor response (TR) and toxicity were assessed. PATIENTS AND METHODS:A total of 107 women were enrolled onto this multicenter, nonrandomized, open-label phase II study. Patients were stratified into first- and second-line treatment groups, based on prior treatment history. Vinorelbine was initially given at 30 mg/m2/wk, with dose modification for toxicity as indicated. Therapy was continued until disease progression or severe toxicity mandated withdrawal or until the patient asked to be removed from the study. RESULTS:The objective response rate for all patients was 34% (95% confidence interval [CI], 25% to 44%): 35% (95% CI, 23% to 48%) for first-line patients and 32% (95% CI, 20% to 47%) for second-line patients. Nine first-line and three second-line patients obtained a complete response (CR). The median duration of objective response was 34 weeks in both groups. The overall survival durations of first- and second-line patients were 67 weeks and 62 weeks, respectively. Granulocytopenia was the predominant dose-limiting toxicity. Two patients died on study as a result of granulocytopenic sepsis. CONCLUSION:Single-agent vinorelbine is an effective and well-tolerated agent for first- and second-line therapy of ABC. The results of this study confirm the findings of similar international trials and suggest vinorelbine should be considered a valid treatment option for patients with ABC and a potential component in future combination regimens for this disease. 10.1200/JCO.1995.13.11.2722
    Vinorelbine: an active, non cross-resistant drug in advanced breast cancer. Results from a phase II study. Terenziani M,Demicheli R,Brambilla C,Ferrari L,Moliterni A,Zambetti M,Caraceni A,Martini C,Bonadonna G Breast cancer research and treatment PURPOSE:To evaluate efficacy and toxicity of vinorelbine and to investigate its cross-resistance with other current drug treatments for metastatic breast cancer. PATIENTS AND METHODS:From July 1992 to December 1993, 57 histologically proven breast cancer patients entered this Phase II study. Patients were stratified according to their status of previous treatment, namely, no prior chemotherapy or relapse more than 12 months since the end of adjuvant chemotherapy (Group A) and other patients (Group B). RESULTS:Fifty three patients were evaluable for response, 27 in Group A and 26 in Group B. All patients were evaluable for toxicity. Vinorelbine was initially administered at the dose of 30 mg/sqm weekly by i.v. infusion in 100 ml of normal saline over 20 minutes. A frequency analysis of drug administration in the first 20 cases revealed two main treatment periodicities, corresponding to one week and to three weeks. Thereafter the drug was administered at 30 mg/sqm on day 1 and 8, every 3 weeks. With the new drug schedule, the mean dose intensity increased from 19.7 to 21.1 mg/sqm per week. Overall, an objective response rate of 47% (95% C.I. 33%-61%) was documented. Four patients achieved complete response (7%, CI: 2%-18%) and 21 partial response (40%, CI: 26%-54%). Fifty nine percent of patients in Group A and 35% in Group B showed objective tumor response. The analysis of response rate in previously treated patients failed to show evidence of cross-resistance with vinorelbine. Main side effects, i.e. neutropenia, local pain, and gastrointestinal and flu-like symptoms, were moderate and short lasting. CONCLUSION:Vinorelbine has clinically significant activity in metastatic breast cancer, and no cross-resistance with prior anthracyclines and CMF treatments. The drug schedule of 30 mg/sqm iv bolus on day 1 and 8 every 3 weeks was found effective and tolerable.
    Phase II trial of weekly IV vinorelbine in first-line advanced breast cancer chemotherapy. García-Conde J,Lluch A,Martin M,Casado A,Gervasio H,De Oliveira C,De Pablo J L,Gorostiaga J,Girón G C,Cervantes A Annals of oncology : official journal of the European Society for Medical Oncology PURPOSE:The study investigated the therapeutic effect of single-agent IV weekly vinorelbine (Navelbine, Pierre Fabre Oncologie, Boulogne, France) a semi-synthetic vinca-alkaloid, in women who had received no prior treatment for advanced or metastatic breast cancer. PATIENTS AND METHODS:Fifty-four patients with assessable advanced or metastatic breast cancer who had received no prior chemotherapy were entered into the study. Fifty patients were evaluable for toxicity and response by WHO criteria; 4 patients were not evaluated because they did not meet the eligibility criteria of the study. Vinorelbine was given as a weekly 30 mg/m2 short IV infusion; and treatment was continued until disease progression or the occurrence of unacceptable toxicity. RESULTS:The overall response rate was 50% (complete response 2%, partial response 48%). The response rate according to target was: lymph nodes 64%; liver 28%; lung 66%; local recurrence 60%. The median duration of response was 9 months, the median time to treatment failure was 5 months and the median survival was 15 months. TOXICITY:Six-hundred thirty cycles were given to 54 patients (53 assessable for tolerance). At least one episode of WHO grade 3/4 granulocytopenia was seen in each of 71% of the patients. Significant nausea/vomiting (WHO grade 3) was seen in less than 1% of cycles and other side effects were uncommon. CONCLUSION:This study confirms that vinorelbine has major single-agent anti-tumour activity as front-line therapy in advanced breast cancer. Given its excellent tolerance profile and low morbidity, it should be considered for inclusion in first-line combination chemotherapy regimens. 10.1093/oxfordjournals.annonc.a059019
    Vinorelbine as single agent in pretreated patients with advanced breast cancer. Barni S,Ardizzoia A,Bernardo G,Villa S,Strada M R,Cazzaniga M,Archili C,Frontini L Tumori Vinorelbine is a new semisynthetic vinca alkaloid with high activity against breast cancer. In this multicenter clinical study we evaluated the activity and toxicity of vinorelbine as a single agent in 30 advanced breast cancer patients pretreated with anthracycline and/or mitoxantrone (24 with recurrent tumor, 6 with non operable cancers). Vinorelbine was given at a weekly dose of 20 mg/m2 for a minimum of 3 weeks. Treatment was continued until there was disease progression or evidence of serious toxicity. Predominant sites of metastasis were viscera (14 cases), soft tissue (11 cases) and bone (5 cases). A median number of 12 doses of vinorelbine (range 3-34) were administered to each patient. Objective responses were recorded in 11 of them and 15 had minimal responses or stable disease. Four patients showed progression of disease during vinorelbine chemotherapy. The median duration of response was 5 months (2-14). The median survival time was 7 months (2-20+): 9 months for responders and 5 months for those with stable or progressive disease. The most important and dose-limiting toxicity was represented by leukopenia. The compliance of patients was very good and the treatment was well accepted by them all including those with low performance status. In conclusion, this study provides further evidence that a weekly schedule with vinorelbine as a single agent is effective and well-tolerated also in pretreated advanced breast cancer patients.
    Phase II study of vinorelbine administered by 96-hour infusion in patients with advanced breast carcinoma. Ibrahim N K,Rahman Z,Valero V,Willey J,Theriault R L,Buzdar A U,Murray J L,Bast R,Hortobagyi G N Cancer BACKGROUND:Vinorelbine given by weekly bolus injection is active and less toxic than bolus vinblastine in the treatment of patients with metastatic breast carcinoma. Vinblastine given by 5-day continuous infusion showed a steep dose-response curve. Pharmacokinetic studies of vinorelbine showed that it is possible to achieve a comparable antitumor effect with a smaller amount of the drug if it is given by continuous infusion. The purpose of this study was to determine the efficacy of vinorelbine given by 96-hour continuous infusion to patients with refractory metastatic breast carcinoma patients. METHODS:Between May 1996 and August 1997, 47 patients with metastatic breast carcinoma were registered into the study. All patients previously had received doxorubicin and 70% had undergone prior paclitaxel treatment. Approximately 56% of the patients had >/=2 metastatic sites. All patients received vinorelbine according to the following dose schedule: 8 mg bolus followed by 11 mg/m(2) by continuous infusion over 24 hours every 4 days every 3 weeks. RESULTS:Forty-four patients were evaluable for response. A total of 193 cycles were administered. The overall response rate was 16% (2 patients achieved a complete response and 5 patients achieved a partial response). The median duration of response was 4.3 months and the median overall survival was 8.6 months. Patients with visceral metastases and/or multiple sites of involvement had shorter durations of response than patients with only soft tissue disease or single-site metastasis (3.1 months vs. 4. 9 months) and shorter overall survival (8.1 months vs. 12 months). Dose reductions were necessary due to cumulative stomatitis and/or fatigue in 12 cycles and neutropenia and/or infection in 13 cycles. CONCLUSIONS:Due to toxicity, a revised maximum tolerated dose for continuous infusion vinorelbine is proposed by the authors: 8 mg intravenously over 10 minutes followed by 10 mg/m(2) by continuous infusion over 24 hours every 4 days. The current dose schedule did not offer an advantage either in response rates or survival over the weekly vinorelbine bolus injection in doxorubicin-resistant and paclitaxel-resistant patients. 10.1002/(sici)1097-0142(19991001)86:7<1251::aid-cncr21>3.0.co;2-f
    Gemcitabine and vinorelbine in pretreated advanced breast cancer: a pilot study. Valenza R,Leonardi V,Gebbia V,Agostara B Annals of oncology : official journal of the European Society for Medical Oncology PURPOSE:Gemcitabine (GEM) and vinorelbine (VNR) are both active against advanced breast cancer (ABC), being able to induce a median ORR of 25% and 40%, respectively. Because of their different mechanism of action and good tolerability, the combination of GEM and VNR has been tested in ABC. PATIENTS AND METHODS:Twenty-nine ABC patients pretreated with anthracycline-taxane were treated with GEM 1000 mg/m2 on day 1, 8, 15, and VNR 25 mg/m2 on day 1 and 8 every twenty-eight days. Analysis of toxicity pattern, response rate, TTP and OS were carried out. RESULTS:Twenty-nine patients were enrolled into the trial. The ORR was 48% (95% CI: 29-67): a CR was observed in three patients (10%; 95% CI: 2-27), while eleven patients (38%; 95 CI: 21-58) achieved PR, eight (28%) had a SD, and seven (24%) progressed. Toxicity was mainly hematological and included: grade 3 leukopenia in 48% of cases without episodes of neutropenic fever, grade 3-4 thrombocytopenia in 10%, and grade 2 anemia in 7%. Non-hematological toxicities were mild and rather infrequent. CONCLUSIONS:The GEM-VNR combination seems to be active in pretreated ABC with an acceptable toxicity pattern, and may well reppresent an interesting therapeutic choice after anthracycline/taxane regimens. 10.1023/a:1008348704373
    Weekly schedule of vinorelbine in pretreated breast cancer patients. Nisticò C,Garufi C,Milella M,Vaccaro A,D'Ottavio A M,Fabi A,Pace A,Bove L,Tropea F,Marsella A,Izzo F,D'Attino R M,Ferraresi V,De Marco S,Terzoli E Breast cancer research and treatment PURPOSE:In this phase II study, we explored tolerability and activity of vinorelbine administered according to a dose-dense weekly schedule with hematopoietic growth factor support in pretreated, advanced breast cancer patients. PATIENTS AND METHODS:From January 1994 to March 1996, 40 patients with metastatic breast cancer, pretreated with at least one prior anthracycline-containing regimen, were entered into the study. PATIENT CHARACTERISTICS:median age 53 years (range 32-70); ECOG performance status 0-1: 34 patients, 2: 6 patients; dominant visceral metastatic disease: 15 patients, dominant non-visceral: 25; anthracycline-refractory/resistant: 2 patients, sensitive: 38 patients. Six patients were treated as first-line therapy for metastatic disease and 34 in second- or subsequent lines. All patients received vinorelbine at the dose of 25 mg/m2/week as a short intravenous infusion, together with routine antiemetic medication. Granulocyte-colony stimulating factor (Lenograstim) at the dose of 150 microg/m2 subcutaneously on day 3 was included in the treatment schedule. RESULTS:The median number of treatment weeks was 23 (range: 4-24), with a delivered dose-intensity (DDI) of 23.8 mg/m2/week (range: 18.7-25, 95.2% of projected dose-intensity). Toxicity was mild, with non-complicated neutropenia being the main toxicity observed (grade 3-4 in 25% of the patients but only 2% of treatment weeks). Overall response rate was 52.5%, with complete responses in 12.5% of patients. Median duration of the response and median time to progression were 10 and 9 months, respectively. Median overall survival was 19 months. CONCLUSION:Dose-dense weekly vinorelbine is safe and effective with minimal toxicity in pretreated advanced breast cancer patients.
    First-line chemotherapy with vinorelbine and paclitaxel as simultaneous infusion in advanced breast cancer. Vici P,Amodio A,Di Lauro L,Conti F,Gionfra T,Belli F,Lopez M Oncology Based on preclinical data showing a synergistic activity of simultaneous administration of vinorelbine and paclitaxel, we carried out a phase II trial in previously untreated advanced breast cancer patients. Treatment consisted of vinorelbine 25 mg/m(2) and paclitaxel 150 mg/m(2), both drugs given by intravenous infusion over 3 h on day 1, with cycles repeated every 3 weeks. Granulocyte colony-stimulating factor, 300 microg subcutaneously, was given on days 7-12 to the first 10 patients. From October 1995 to January 1997, 43 patients with advanced breast cancer entered the study, and 41 were evaluable for response. We obtained 2 complete responses (5%) and 18 partial responses (44%), for an overall response rate of 49% (95% CI 34-64%). Median time to response, time to progression and survival were 2, 7 and 22 months, respectively. Myelosuppression was the dose-limiting toxicity, with G4 neutropenia in 21% and neutropenic fever in 7% of the patients. Other toxicities were mild. Simultaneous infusion of vinorelbine and paclitaxel is a well-tolerated and active regimen in metastatic breast cancer, with overall results similar to those reported with more toxic regimens; furthermore, it may be a good option in patients with anthracycline contraindications. 10.1159/000012071
    Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older. Vogel C,O'Rourke M,Winer E,Hochster H,Chang A,Adamkiewicz B,White R,McGuirt C Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Older patients with advanced breast cancer are less likely to receive chemotherapy than younger patients. Vinorelbine is an attractive alternative in this setting because of its clinical activity and low frequency of side effects. This multicenter, phase II trial was designed to assess the safety and efficacy of intravenous vinorelbine as first-line therapy in women > or = 60 years old. PATIENTS AND METHODS:Fifty-six women (median age, 72 years; range 60-84 years), with measurable advanced breast cancer and no prior chemotherapy for metastatic disease, were enrolled and included in the analysis. Vinorelbine 30 mg/m2 was administered weekly for 13 weeks and then every two weeks until development of progressive disease; doses were reduced or delayed to manage toxicity. RESULTS:The objective response rate was 38% (95% confidence interval (95% CI): 24%-51%); median duration of response, nine months; median time to disease progression in all patients, six months. The major dose-limiting toxicity was hematologic, which led to a median dose intensity of 20.6 mg/m2/week. Grade 3-4 nonhematologic toxicity consisted of asthenia (7%); nausea and generalized pain (5%); vomiting, chest pain, abdominal pain, and elevated AST (4%); fever, diarrhea, constipation, and injection site reaction (2%). Neurotoxicity and alopecia were grade 1-2 and relatively infrequent. CONCLUSIONS:Vinorelbine offers a promising alternative for the management of advanced breast cancer in elderly patients who are concerned about the subjective side effects of cytotoxic chemotherapy. The dose-limiting toxicity is neutropenia, which is readily managed with dose adjustment. Nonhematologic toxicity, including gastrointestinal side effects, is minimal. Randomized studies are warranted to compare the activity of vinorelbine with that of other regimens in elderly patients. 10.1023/a:1008364222793
    Phase I study of vinorelbine by 96-hour infusion in advanced metastatic breast cancer. Ibrahim N K,Valero V,Theriault R L,Willey J,Walters R S,Buzdar A U,Booser D J,Hortobagyi G N American journal of clinical oncology The purpose of this study was to evaluate the maximum tolerated dose and the toxicity profile of vinorelbine administered by continuous infusion for 96 hours to patients who had received prior chemotherapy for metastatic breast cancer. Forty-three patients with metastatic breast cancer were treated with vinorelbine 8 mg intravenously for 10 minutes (day 1) followed by continuous infusion of vinorelbine for 96 hours. Treatments were repeated every 3 weeks. Eighty-eight percent of the patients had had two or more prior chemotherapeutic regimens: 91% had prior doxorubicin therapy and 77% had prior paclitaxel therapy. All 43 patients were evaluable for toxicity. The median age was 49 years. All patients had a performance status less than or equal to 2 and a life expectancy more than 12 weeks. Eight dose levels were evaluated, and a total of 182 cycles were given. National Cancer Institute grade III or IV granulocytopenia was observed in 64 (35%) cycles, neutropenic fever in 27 (15%) cycles, fatigue (National Cancer Institute grade III or IV) in 18 (10%) cycles, and hand-foot syndrome in 8 (4%) cycles. In 17 (9%) cycles, patients were hospitalized. The maximum tolerated dose of this regimen was determined to be vinorelbine 8 mg intravenously for 10 minutes (day 1) followed by continuous vinorelbine infusion 11 mg/m2 for 96 hours. The dose-limiting toxicity was neutropenic fever and stomatitis.
    Phase I dose-finding and pharmacokinetic study of docetaxel and vinorelbine as first-line chemotherapy for metastatic breast cancer. Campone M,Fumoleau P,Delecroix V,Deporte-Fety R,Perrocheau G,Vernillet L,Borg-Olivier O,Louboutin J P,Bissery M C,Riva A,Azli N Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND AND PURPOSE:Anthracycline-containing regimens are widely used in advanced breast cancer. However, there is a need for new, non-anthracycline regimens that are active in patients for whom anthracyclines are contraindicated. The aim of this study was to determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs) and recommended doses of docetaxel and vinorelbine as first-line chemotherapy in patients with metastatic breast cancer. The pharmacokinetics of both drugs was also evaluated. PATIENTS AND METHODS:Thirty-four women with first-line metastatic breast cancer were treated with docetaxel, 60-100 mg/m2 (day 1), and vinorelbine, 20-22.5 mg/m2 (days 1 and 5), repeated every three weeks and administered on an outpatient basis. RESULTS:Two MTDs were determined: MTD1 was defined at the dose level using docetaxel 75 mg/m2, and vinorelbine 22.5 mg/m2 DLT being a grade 3 stomatitis that was more related to the dose of vinorelbine than that of docetaxel. Therefore, the study continued with a fixed dose of vinorelbine, 20 mg/m2, and docetaxel 85-100 mg/m2. MTD2 was defined at the dose level combining docetaxel, 100 mg/m2, and vinorelbine, 20 mg/m2; DLTs were grade 3 stomatitis and severe asthenia. Fluid retention was observed in 41% of patients but was never severe or a reason for patient discontinuation. In comparison with historical experience, Daflon 500 did not seem to increase the efficacy of the three-day corticosteroid premedication by further reducing the incidence or severity of fluid retention. No significant neurotoxicity was observed and no patient discontinued the study due to this site effect. Activity was observed at all dose levels and at all metastatic sites, with an overall response rate of 71% (95% CI: 52.0%-85.8%). The median time to progression was 31.4 weeks (95% CI: 12-48 weeks) and median survival was 15.6 months (95% CI: 2.6-26.6 months). The pharmacokinetics of docetaxel and vinorelbine were not modified between day 1 and day 3 when the two drugs were combined with the day 1 administration schedule used in this study. CONCLUSION:The recommended doses for phase II studies are docetaxel, 75 mg/m2 (day 1), plus vinorelbine, 20 mg/m2 (days 1 and 5), repeated every three weeks. At these doses, the combination was found to be active and well tolerated. 10.1023/a:1011133410652
    Weekly docetaxel plus gemcitabine or vinorelbine in refractory advanced breast cancer patients: a parallel dose-finding study. Southern Italy Cooperative Oncology Group (SICOG). Frasci G,Comella P,D'Aiuto G,Thomas R,Capasso I,Elmo M,Botti G,Cortino G R,Lapenta L,De Rosa V,Vallone P,Petrillo A,Comella G Annals of oncology : official journal of the European Society for Medical Oncology PURPOSE:The objective of this study was to determine the docetaxel MTD when combined with gemcitabine or vinorelbine in advanced breast cancer patients who had received previous anthracycline-based chemotherapy for advanced disease. PATIENTS AND METHODS:Advanced breast cancer patients aged between 18 and 70 with ECOG PS 0-2 who had not responded to, or had relapsed after, first-line anthracycline-based chemotherapy, were randomized to receive either gemcitabine 1000 mg/m2 or vinorelbine 25 mg/m2 in combination with escalating doses of docetaxel (starting from 30 mg/m2), all on days 1 and 8 every three weeks. Escalation was stopped if > 33% of patients treated at a given dose level showed DLT at the first cycle. RESULTS:A total of 34 patients with locally advanced (8) or metastatic disease (26) were treated, for a total of 94 cycles delivered. Nineteen patients received docetaxel in combination with gemcitabine and 15 with vinorelbine. All patients had been pretreated with anthracyclines, and 24 of 34 had also received weekly dose-dense paclitaxel. A docetaxel dose of 40/m2 proved to be safe when combined on days 1 and 8 with gemcitabine, while a dose of 35 mg/m2 was tolerated in combination with vinorelbine. Overall, nine episodes of DLT, all of them neutropenia, occurred at the first cycle. Considering all 94 cycles, grades 3 or 4 neutropenia and thrombocytopenia occurred in 15 (44%), and 7 (20%) patients. Non-hematologic toxicity was mild, except for three cases of grade 2 peripheral neuropathy. All patients were assessed for response on an 'intent-to-treat' basis. Overall, five partial responses were recorded (docetaxel + gemcitabine = 3 and docetaxel + vinorelbine = 2), for a 15% (95% CI: 5%-31%) overall response rate. Only 1 of 24 (4%) patients who had received weekly dose-dense paclitaxel responded to treatment. CONCLUSIONS:The weekly docetaxel administration in combination with either gemcitabine or vinorelbine is a well-tolerated treatment for heavily pretreated advanced breast cancer patients. This approach, although sometimes capable of achieving a major response, does not seem advisable in advanced breast cancer patients refractory to both anthracyclines and paclitaxel. 10.1023/a:1008346708604
    Impact of an all-oral capecitabine and vinorelbine combination regimen on functional status of elderly patients with advanced solid tumours: A multicentre pilot study of the French geriatric oncology group (GERICO). Rousseau F,Retornaz F,Joly F,Esterni B,Abadie-Lacourtoisie S,Fargeot P,Luporsi E,Servent V,Laguerre B,Brain E,Geneve J, Critical reviews in oncology/hematology BACKGROUND:Elderly metastatic cancer patients typically have short life expectancy and frequently suboptimal treatment. Goals of therapy should include preservation of functional status as well as clinical response. For elderly patients, oral chemotherapy could be a valuable strategy, avoiding the constraints and risks of intravenous drugs. METHODS:This study assessed effect of an all-oral combination of capecitabine and vinorelbine on functional status (measured by basic Activities of Daily Living [ADL]), toxicity, efficacy and compliance in patients ≥70 years with advanced breast, prostate or lung cancer. RESULTS:Eighty patients were enrolled. After three cycles, 81.8% of patients had stabilised or improved ADL, and 8.6% and 42.9% had a response or stabilised disease. Compliance was excellent (68.8%). The most common grade 3-4 toxicities were haematological (17.9%) and gastrointestinal (7.7%). CONCLUSION:In elderly cancer patients, an all-oral combination of capecitabine and vinorelbine maintains functional status, is well tolerated, and provides good disease control. 10.1016/j.critrevonc.2009.12.003
    First line combination chemotherapy with docetaxel and vinorelbine in advanced breast cancer. A phase II study. Pectasides D,Dimopoulos M A,Aravantinos G,Kalophonos H P,Papacostas P,Briasoulis E,Cogas E,Papadimitriou C,Skarlos D,Kosmidis P,Fountzilas G Anticancer research UNLABELLED:We evaluated the efficacy and tolerance of the combination of docetaxel and vinorelbine as first line treatment in metastatic breast cancer (MBC). These agents have different mechanisms of action and both are active in advanced breast cancer. Thirty-nine chemotherapy-naive for metastatic disease patients were treated on an out-patient basis with vinorelbine 20 mg/m2 i.v. on days 1 and 8 and docetaxel 85 mg/m2 i.v. on day 8, every 3 weeks. Twenty-one (53.8%) patients had locoregional disease, 30 (76.9%) had distant metastases and 20 (51.3%) had visceral metastases. The intent-to-treat objective response rate (RR) was 48.75% (19 out of 39 patients; 95% confidence interval (CI), 32.4% to 65.2%). Four patients (10.25%) achieved a complete response (CR) (95% CI, 2.9% to 24.2%) and 15 (38.5%) a partial response (PR) (95% CI, 23.4% to 55.4%). The median duration of response was 4 months, the median time to progression (TTP) was 6 months and the median survival-time was 11.3 months. Grade 3 and/or 4 (3/4) anemia and thrombocytopenia occurred in 7.7% and 5.1% of patients, respectively. Twelve (30.7%) patients developed grade 3/4 neutropenia and 7 (17.9 %) were complicated with fever. Grade 3/4 diarrhea, nausea-vomiting, fatigue and constipation were not a problem. Alopecia was universal. Grade 3/4 neurotoxicity was evident in 2.6% of patients. None of the patients developed allergic reaction or fluid retention. There was one treatment-related death due to grade 4 neutropenia and sepsis. CONCLUSION:This combination of docetaxel and vinorelbine, a non-anthracycline-containing regimen, is a moderately effective regimen for the treatment of chemotherapy-naive breast cancer patients with metastases, causing only mild to moderate toxicity.
    Capecitabine in the routine treatment of advanced breast cancer: results from a non-interventional observational study in 876 [corrected] patients. Siedentopf Friederike,Gohler Thomas,Hesse Tobias,Nusch Arud,Sulberg Heiko Onkologie BACKGROUND:This observational study evaluated patient characteristics, treatment schedule and setting, efficacy and tolerability of capecitabine in routine clinical practice in Germany. PATIENTS AND METHODS:Patients with advanced breast cancer pretreated with or ineligible for anthracycline-containing therapy were treated with capecitabine. Data were collected until disease progression or completion of 12 cycles (with long-term follow-up in progression-free patients). RESULTS:846 of the 876 [corrected] patients enrolled between 2002 and 2007 were eligible. Capecitabine was administered as monotherapy in 64% (median starting dose 1,070 mg/m(2) bis in diem (b.i.d.)) and combination chemotherapy (typically with vinorelbine or docetaxel) in 36% (median starting dose 987 mg/m(2) b.i.d.). Capecitabine was given as first-line therapy in 35% of patients. Objective response rate was 41% and median progression-free survival was 7.5 months. Good performance status at baseline was a significant predictor of efficacy. The most common non-hematological toxicity was hand-foot syndrome (all grades: 54%; grade 3: 7%). Myelosuppression and alopecia were substantially less common with capecitabine monotherapy than with capecitabine combination regimens. CONCLUSIONS:Capecitabine, alone or in combination, is a feasible, effective treatment for breast cancer. Our findings in real-life clinical practice compare favorably with results from interventional studies, perhaps reflecting the longer treatment duration possible at more tolerable doses. 10.1159/000242219
    Vinorelbine With Capecitabine, an Evergreen Doublet for Advanced Breast Cancer: A Systematic Literature Review and Pooled-Analysis of Phase II-III Studies. Petrelli Fausto,Di Cosimo Serena,Lonati Veronica,Barni Sandro Clinical breast cancer Metastatic breast cancer (MBC) is treated with cytotoxic drugs or endocrine agents according to the site and extent of the disease, biology, previous treatments, and the patient's condition, comorbidities, and wishes. In MBC, vinorelbine (VRB) and capecitabine (X; VRB + X) are chemotherapy drugs that hold activity as first or later lines of therapy. We conducted a systematic literature review and meta-analysis to quantify the efficacy of the VRB + X combination in HER2-negative (HER2) MBC. We searched PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library, and CINAHL for phase II/III clinical trials that assessed VRB + X for patients with HER2 MBC. Pooled estimates of the overall response rate (RR), median progression-free survival (PFS), and overall survival (OS) were computed using random or fixed effects models. Twenty-seven studies were included in the analysis, encompassing a total of 1356 MBC patients. All were phase II (n = 21) or prospective/pilot (n = 5) trials, except for 1 that was a phase III controlled trial. The pooled estimate for the RR in first-line therapy (n = 16 trials) was 52.9% (95% confidence interval [CI], 46.5%-59.2%). For second-line trials, data were available in n = 9 studies and the overall RR was 41% (95% CI, 31.2%-51.6%). The pooled estimates for median PFS and OS in first-line therapy were 7.3 (95% CI, 6.2-8.3) and 22.3 (95% CI, 20-24.5) months, respectively. Vinorelbine + X, with the dose and schedules currently used in clinical practice, appears to be an effective and feasible chemotherapy for MBC, for first- and also for second-line therapy. 10.1016/j.clbc.2016.05.002
    Phase II trial of biweekly administration of vinorelbine and gemcitabine in pretreated advanced breast cancer. Stathopoulos George P,Rigatos Sotiris K,Pergantas Nikos,Tsavdarides Dimitris,Athanasiadis Ilias,Malamos Nikos A,Stathopoulos John G Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:To determine the efficacy of gemcitabine (GEM) plus vinorelbine (VRL) administered biweekly in pretreated patients with advanced breast cancer. PATIENTS AND METHODS:Advanced breast cancer patients without response, with stable disease, or with recurrence within 6 months of prior treatment were given GEM 1,000 mg/m(2) and VRL 25 mg/m(2), once every 2 weeks for at least six cycles. RESULTS:Of the 51 patients enrolled, 50 (median, age 58 years; range, 34 to 76 years) were assessable. All patients had prior chemotherapy with an anthracycline-related regimen that included taxanes in 50% of the cases. Four patients (8%) had a complete response (CR) and 23 (46%) had a partial response (PR), for an overall response rate of 54%; 16 (32%) had stable disease and 7 (14%) experienced disease progression. Response occurred mainly in patients with soft tissue (83.3%) and lung metastasis (66.7%). Response duration was 4 to 8+, 4 to 9+, and 4 to 9 months for those with CR, PR, and stable disease, respectively. The regimen was well tolerated, with grade 1 to 2 myelotoxicity and asthenia reported. No patient required a dose reduction. Gastrointestinal side effects were negligible. Patients received 99.7% (range, 93.0% to 100.0%) of the planned dose-intensity of each drug. CONCLUSION:GEM in combination with VRL is an active regimen for advanced breast cancer patients, and biweekly administration significantly reduces myelotoxicity. 10.1200/JCO.2002.20.1.37
    Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy. Freyer G,Delozier T,Lichinister M,Gedouin D,Bougnoux P,His P,Imadalou K,Trillet-Lenoir V Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:A phase II trial was performed to evaluate the efficacy, tolerance, and pharmacokinetic profiles of oral vinorelbine (Navelbine). Oral Navelbine (NVB; Pierre Fabre Médicament, Boulogne, France) was given as first-line chemotherapy for locally advanced or metastatic breast carcinoma (ABC). PATIENTS AND METHODS:Sixty-four patients were entered to receive oral NVB on a weekly basis for a total of 8 weeks unless progression or toxicity occurred. Oral NVB was given at 60 mg/m(2) weekly for the first three administrations and was increased to 80 mg/m(2) for the subsequent administrations if there was no grade 4 neutropenia or no more than one episode of grade 3 neutropenia. Patients with objective response or stable disease continued treatment up to a total of 12 weeks or more. RESULTS:Fifty-eight evaluable patients were included in our study. Four patients (6.9%) had complete responses, and 14 (24.1%) had partial responses, for an overall response rate of 31% (95% CI, 19% to 43%). Median progression-free survival was 17.4 weeks. Median overall survival is not yet reached. There were no treatment-related deaths. The main toxicity was neutropenia: grade 4 in 17.2% of the patients, and 1.8% of administrations and associated clinical serious events in 4 patients (6.2%). Grade 3 and 4 nausea and/or vomiting were noted in 3.1% and 4.6% of the patients, respectively. Only one patient developed grade 3 neuroconstipation. An analysis of Quality of Life Questionnaire C30 forms revealed no significant alteration between baseline and weeks 8 and 16 in global quality of life. CONCLUSION:Oral NVB at this schedule is an effective and well-tolerated agent in the treatment of ABC and offers a promising alternative to the intravenous route. Combination studies are ongoing. 10.1200/jco.2003.09.057
    Weekly combination of docetaxel and vinorelbine in metastatic breast cancer: a phase I/II study. Cals L,Nouyrigat P,Valenza B,Pedinelli F J,Juin P Oncology OBJECTIVE:A phase I/II study was carried out to determine the recommended dose (RD) and to assess the efficacy and safety of a weekly docetaxel-vinorelbine combination in advanced breast cancer (ABC) patients. METHODS:Twenty-four female patients with histologically proven ABC received intravenous vinorelbine (20 min) followed by intravenous docetaxel (1 h) on days 1, 8 and 15 of a 4-week cycle. Starting doses were 20 mg/m2 docetaxel and 15 mg/m2 vinorelbine. RESULTS:Patients had a median age of 62 years (range 38-74 years), and 92% had performance status 0-1. The most common sites of metastases were the lungs (32%), liver (29%) and bone (14%). Seventy-one percent of patients had received prior chemotherapy. The RDs of docetaxel and vinorelbine were 20 and 15 mg/m2, respectively. Dose-limiting toxicities were neutropenia-induced dose delay and febrile neutropenia. The response rate at the RD was 43%. All responses were seen in non-pretreated patients. Grade 3-4 neutropenia occurred in 80% of patients, 3 of whom experienced febrile neutropenia and died as a possible consequence of neutropenia. CONCLUSION:This docetaxel-vinorelbine combination as first-line therapy yields a response rate similar to that of single-agent docetaxel as second-line therapy. However, given the high rate of myelotoxicity, higher doses are not feasible. 10.1159/000081326
    A phase I study of capecitabine in combination with vinorelbine in advanced breast cancer. Lorusso Vito,Crucitta Enrico,Silvestris Nicola,Guida Michele,Misino Andrea,Latorre Agnese,De Lena Mario Clinical breast cancer A phase I study was conducted in order to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the combination of vinorelbine and capecitabine in patients affected with metastatic breast cancer. Eighteen patients with histologically confirmed advanced breast cancer, who had failed =1 prior chemotherapy regimen, were enrolled. The median age was 56 years (range, 39-70 years). All but 1 had previously received a combination of anthracyclines and taxanes; performance status (Eastern Cooperative Oncology Group) was 0/1 or 2 in 13 and 5 patients, respectively. Vinorelbine was administered at a fixed dosage of 25 mg/m2 on days 1 and 8 every 3 weeks. Capecitabine was administered orally, at an escalated dose ranging from 1400 mg/m2 to 2250 mg/m2 for 14 consecutive days starting on day 1 of the cycle, divided into 2 daily doses delivered half an hour after eating at 12-hour intervals. Three patients were treated at each dose level: if 1 patient developed a DLT, an additional 3 patients were treated at the same dose level. If 2 additional patients experienced DLT, no further escalation was allowed and the previous dose level was declared MTD. Dose-limiting toxicity was reached at 2250 mg/m2 of capecitabine with 3 out of 3 patients experiencing grade 4 neutropenia plus grade 3 diarrhea and grade 3 oral mucositis in 1 patient). Thus, MTD was defined at 2000 mg/m2 capecitabine. Other observed grade 2 side effects were: 1 patient with neutropenia, 1 with hand-foot syndrome, 2 with mucositis, 1 with cutaneous rash, and 1 with thrombocytopenia. With regard to response rate, we observed 1 complete response (5.5%), 6 partial responses (33%), and 4 disease stabilizations (22%). The median time to progression was 12 weeks and the median survival 41 weeks. The MTD of capecitabine in combination with vinorelbine at 25 mg/m2 dosage on days 1 and 8 of a 3-week schedule is 2000 mg/m2/day for 14 consecutive days. Moreover, this regimen showed interesting activity with 61% overall disease control (complete plus partial response plus disease stabilization) in patients pretreated with anthracyclines and taxanes warranting further investigations in a large, multicenter phase II study. 10.3816/cbc.2003.n.019
    Docetaxel plus vinorelbine as salvage chemotherapy in advanced breast cancer: a phase II study. Rodríguez Javier,Calvo Emiliano,Cortes J,Santisteban Marta,Perez-Calvo J,Martínez-Monge Rafael,Brugarolas Antonio,Fernández-Hidalgo Oscar Breast cancer research and treatment PRECIS:Administration of a combined regimen of docetaxel plus vinorelbine every 4 weeks is feasible and shows activity in heavily pretreated patients with advanced breast cancer. PURPOSE:To determine the activity and tolerance of docetaxel plus vinorelbine in heavily pretreated patients with advanced breast cancer. METHODS:Thirty-five metastatic breast cancer patients with ECOG performance status of 0-2 received docetaxel (80 mg/m2 given intravenously) on day 1 and vinorelbine (30 mg/m2 given intravenously) on days 1 and 14, every 4 weeks. The median number of prior chemotherapy regimens was 2 (range: 1-4). Twenty-five patients (71.4%) had been treated previously using intensive therapy approaches with peripheral blood-derived stem cell (PBSC) support, including high-dose chemotherapy (11 patients), multicyclic dose-intensive chemotherapy supported with repeated PBSC infusions (seven patients), or both (seven patients). Twenty-eight patients (80%) received previous chemotherapy for metastatic disease. Adjuvant therapy in the remaining seven patients consisted of high-dose chemotherapy and PBSC support or an anthracycline-containing regimen. RESULTS:The total number of courses was 229, and the median number of courses per patient was 6 (range: 1-16). There was one toxic death (2.8%). Grade 3-4 toxicities included mucositis (17.1%), neutropenia (37.1%), anemia (5.7%), vomiting (2.9%), and asthenia (14.3%). Eighteen patients (58%; 95% CI: 40.6-75.4%) achieved an objective response, including four complete responses (12.9%) and 14 partial responses (45.1%). Overall response rate was 51.4% (95% CI: 34.8-67.9%). After a median follow-up of 20 months (range: 2-42), overall survival was 20 months (95% CI: 16-24), and median time to progression was 13 months (95% CI: 7-19). CONCLUSION:This combination shows activity and an acceptable toxicity profile in patients with advanced breast cancer.
    Sequential docetaxel followed by epirubicin-vinorelbine as first-line chemotherapy in advanced breast cancer. Vici Patrizia,Foggi Paolo,Colucci Giuseppe,Capomolla Elisabetta,Brandi Mario,Giotta Francesco,Gebbia Nicola,Di Lauro Luigi,Valerio Maria Rosaria,Paoletti Giancarlo,Belli Franca,Pizza Carmine,Giannarelli Diana,Lopez Massimo Anticancer research BACKGROUND:This phase II study evaluated the efficacy and the tolerability of a sequential regimen of docetaxel followed by epirubicin-vinorelbine combination as first-line chemotherapy in advanced breast cancer. PATIENTS AND METHODS:Twenty-seven patients received docetaxel 100 mg/m2 (4 cycles) followed by 4 cycles of epirubicin 90 mg/m2 (day 1) combined with vinorelbine 25 mg/m2 (days 1 and 5), with cycles repeated every 3 weeks. G-CSF was administered during epirubicin-vinorelbine treatment. RESULTS:There were 1 (3.7%) CR and 14 (51.9%) PR, for an overall response rate of 55.6% (95% CI, 36.9%-74.3%). Median time to response, time to progression and overall survival were 2, 9 and 25 months, respectively. The dose-limiting toxicity was neutropenia (grade 3 to 4 in 85% of the patients). There was one toxic death due to neutropenic fever. Gastrointestinal side-effects were generally mild According to the Simon two-stage design the response rate was considered unsatisfactory and patient accrual was terminated. CONCLUSION:This sequential regimen appears to be moderately effective; possibly, a modulation of the treatment based on objective responses instead of a fixed number of cycles may be more appropriate in order to obtain better results.
    Phase I study of continuous and intermittent schedules of lapatinib in combination with vinorelbine in solid tumors. Chew H K,Somlo G,Mack P C,Gitlitz B,Gandour-Edwards R,Christensen S,Linden H,Solis L J,Yang X,Davies A M Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Chemotherapy in combination with small-molecule epidermal growth factor receptor inhibitors has yielded inconsistent results. Based on preclinical models, we conducted a phase I trial of two schedules of lapatinib and vinorelbine. PATIENT AND METHODS:Patients had advanced solid tumors and up to two prior chemotherapeutic regimens. Patients were enrolled on two dose-escalating schedules of lapatinib, continuous (arm A) or intermittent (arm B), with vinorelbine on days 1, 8, and 15 of a 28-day cycle. Tumors from a subset of patients were evaluated for gene mutations and expression of targets of interest. RESULTS:Fifty-one patients were treated. The most common grade 3/4 toxic effects included leukopenia, neutropenia, and fatigue. Dose-limiting toxic effects were grade 3 infection, febrile neutropenia, and diarrhea (arm A) and bone pain and fatigue (arm B). The maximum tolerated dose was vinorelbine 20 mg/m(2) weekly and lapatinib 1500 mg daily (arm A) and vinorelbine 25 mg/m(2) weekly and lapatinib 1500 mg intermittently (arm B). One patient on each arm had a complete response; both had human epidermal growth factor receptor 2-positive breast cancer. In a subset of patients, lack of tumor PTEN expression correlated with a shorter time to progression. CONCLUSION:In an unselected population, two schedules of lapatinib and vinorelbine were feasible and well tolerated. 10.1093/annonc/mdr328
    A phase II study of epirubicin, vinorelbine and cisplatin in advanced breast cancer. Garrone Ornella,Principe Ernesto,Occelli Marcella,Mercuri Michelangelo,Numico Gianmauro,Granetto Cristina,Di Costanzo Gianna,Rattazzi Pier Dino,Merlano Marco Anti-cancer drugs Our objective was to evaluate the activity and safety of the combination of cisplatin, epirubicin and vinorelbine (CEV) in advanced breast cancer patients. Patients with advanced breast cancer, locally advanced or metastatic, received epirubicin 75 mg/m2 and cisplatin 50 mg/m2 on day 1, and vinorelbine 25 mg/m2 on day 8. Cycles were repeated every 3 weeks. A total of 35 patients were treated. Thirty-one patients were evaluated for response. One hundred and fifty-five cycles of chemotherapy were administered overall. The objective response rate (ORR) was 84%, including complete response in 13% of patients. All stage III patients achieved a downstaging, with a pathological complete response in two out of 10 patients. Patients with stage IV disease obtained objective response in 67% of cases. Toxicity was mild to moderate. The most common grade 3-4 adverse event was febrile neutropenia, which occurred in 17% of patients. We conclude that CEV combination represents an effective treatment for patients with previously untreated advanced breast cancer, allowing an important ORR. Moreover this regimen appears to be well tolerated.
    Phase III study of intravenous vinorelbine in combination with epirubicin versus epirubicin alone in patients with advanced breast cancer: a Scandinavian Breast Group Trial (SBG9403). Ejlertsen Bent,Mouridsen Henning T,Langkjer Sven T,Andersen Jorn,Sjöström Johanna,Kjaer Mogens, Journal of clinical oncology : official journal of the American Society of Clinical Oncology PURPOSE:To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. PATIENTS AND METHODS:A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m(2) on day 1 and vinorelbine 25 mg/m(2) on days 1 and 8, or epirubicin 90 mg/m(2) IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1000 mg/m(2) (950 mg/m(2) from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. RESULTS:Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P =.15). The complete response rate was significantly superior in the combination arm (17% v 10%; P =.048) as was median duration of progression-free survival (10.1 months v 8.2 months; P =.019). Median survival was similar in the two arms (19.1 months v 18.0 months; P =.50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. CONCLUSION:Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival. 10.1200/JCO.2004.11.503
    Full dose paclitaxel plus vinorelbine as salvage chemotherapy in anthracycline-resistant advanced breast cancer: a phase II study. Polyzos A,Tsavaris N,Kosmas C,Gogas H,Toufexi H,Kosmidis C,Markopoulos C,Giannopoulos A,Papadopoulos O,Stamatiadis D,Kouraklis G Journal of chemotherapy (Florence, Italy) This phase II trial studied the efficacy and toxicity of full dose paclitaxel plus vinorelbine, as salvage chemotherapy in patients with metastatic breast cancer resistant to anthracyclines. Patients received vinorelbine (30 mg/m2) followed 1 hour later by full dose paclitaxel (175 mg/m2) every 3 weeks for a maximum of 8 cycles or until disease progression. Because of the heavy pretreatment of the patients, prophylactic granulocyte-colony stimulating factor (5 microg/kg) was administered daily for 5-10 days. To minimize potentially cumulative neurotoxicity due to both agents, amifostine was given prior to chemotherapy. Thirty-four patients: 8 with tumors primary resistant and 26 with tumors recurring within 3-6 months after anthracycline treatment, were evaluable for efficacy and toxicity. Objective responses occurred in 11 patients [32%; 95% confidence interval (CI): 16.3-47.7%), all partial responses. Responses were observed in lung and liver. The median response duration was 4 months (range 3-7), median time to progression was 5 months (range 3-9) and median overall survival was 8 months (range 4-24). Neutropenia was dose limiting (35% grade 3-4 toxicity). The left ventricular ejection fraction, measured and followed in 18 patients, fell less than 20% below baseline level in 9 patients (50%), but only one patient developed congestive cardiac failure. The paclitaxel-vinorelbine regimen was moderately tolerated and moderately effective in poor prognosis breast cancer patients with visceral metastases and tumors resistant to anthracyclines. The combination at these doses and schedules should be considered in the design of regimens for advanced breast cancer. 10.1179/joc.2003.15.6.607
    Phase II study of paclitaxel combined with vinorelbine in patients with advanced breast cancer. Spano Jean Philipe,Bouillet Thierry,Boaziz Catherine,Piperno-Neumann Sophie,Brunel Pascale,Hennebelle Frédéric,Amsalhem Patricia,Brunet-Pommeyrol Arlette,Kanoui Aimé,Morin Franck,Breau Jean Luc,Morere Jean François American journal of clinical oncology Paclitaxel and vinorelbine are two drugs active against breast cancer. A phase II study was initiated with the aim of assessing the efficacy and feasibility of the combination. Twenty-six patients presenting with advanced breast cancer with a taxane- and vinorelbine-free line of chemotherapy were included and treated with vinorelbine (20 mg/m2 on D1, D15), followed by paclitaxel (175 mg/m2 on D1), every 3 weeks. A 48% (95% CI: 35-61) response rate was obtained in the 23 patients evaluable for response. Vinorelbine was administered on D15, as scheduled, in 72% of cycles. The main toxicity observed was grade III to IV neutropenia in 73% of patients. Febrile neutropenia was reported in three patients. Disease-free survival was 118 days, and overall median survival was 361 days. This combination of paclitaxel and vinorelbine is feasible and effective in patients with early relapse or previously treated with first-line chemotherapy for metastatic disease.
    Treatment of metastatic breast cancer with vinorelbine and docetaxel. Savio Giuseppina,Laudani Agata,Leonardi Vita,Pepe Alessio,Scianna Caterina,Gebbia Vittorio,Agostara Biagio American journal of clinical oncology OBJECTIVE:A phase II study was performed to evaluate efficacy and safety of the combination vinorelbine and docetaxel in patients with metastatic breast cancer previously treated with anthracycline-based regimens. Overall 41 patients were included in the study. METHODS:Treatment consisted of vinorelbine 25 mg/m2 and docetaxel 75 mg/m2, both administered on day 1 every 3 weeks for a maximum of 9 cycles. Most patients (92%) were postmenopausal with a median age of 57 years, and median ECOG performance of 1. Sites of disease were viscera in 42% of patients, bones in 30%, soft-tissues in 32%. Sixty-five percent of patients had >2 metastatic sites. Previous treatments included neo-adjuvant chemotherapy in 7.3% of cases, adjuvant chemotherapy in 71%, and front-line chemotherapy for advanced disease in 50% of cases. RESULTS:A total of 273 cycles of chemotherapy were delivered (mean 6 cycles/patient). All patients were assessable for toxicity: alopecia was recorded in all patients, grade 2-3 neutropenia in 34% and grade 4 in 9.7%; grade 2-3 nausea/vomiting in 29%, grade 2-3 mucositis in 24.3%. Out of 39 patients evaluable for response, 7 (18%) complete responses and 13 (33%) partial responses have been recorded with an overall response rate of 51%. Six patients (15%) experienced stable disease and 13 patients (33%) progressed. Mean duration of responses was 15.2 months. Median time to progression and median overall survival were 6.2 and 14 months, respectively. CONCLUSION:In patients with metastatic breast cancer previously treated with anthracyclines the combination vinorelbine-docetaxel is very active and well tolerated representing a valid therapeutic option for the management of this patient population. 10.1097/01.coc.0000215456.56584.fc
    Cisplatin and vinorelbine (PVn) for the treatment of advanced breast cancer: 10 years of experience. Shamseddine Ali,El-Saghir Nagi,Chehal Aref,Saliba Teddy,Taher Ali Le Journal medical libanais. The Lebanese medical journal Breast cancer is the most common malignancy in women throughout the world. It is the leading cause of cancer death of women aged > 50 years. Cisplatin and vinorelbine are active as single agents in advanced breast cancer but their combination was not studied before. We conducted three phase II trials using this combination in advanced breast cancer. Hereby, we describe our experience over a 10-year period at the American University of Beirut using this combination in metastatic disease as 1st and 2nd line therapy as well as in the neoadjuvant setting in patients with locally advanced disease. Our data will be compared with other groups using the same regimen for the management of advanced breast carcinoma.
    Capecitabine and vinorelbine in elderly patients (> or =65 years) with metastatic breast cancer: a phase I trial (SAKK 25/99). Hess D,Thürlimann B,Pagani O,Aebi S,Rauch D,Ballabeni P,Rufener B,Castiglione-Gertsch M,Goldhirsch A, Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Few chemotherapy regimens are suitable for the treatment of elderly patients with advanced breast cancer. With the aim of finding a regimen with a low burden of subjective non-overlapping toxic effects, vinorelbine and capecitabine were chosen to be investigated in a phase I dose-finding study. PATIENTS AND METHODS:Thirty-six patients with advanced breast cancer were stratified for the presence of bone and non-bone involvement and treated at four dose levels from capecitabine 800 mg/m2 orally days 1-14 and vinorelbine 20 mg/m2 intravenously days 1 and 8, to capecitabine 1250 mg/m2 orally days 1-14 and vinorelbine 25 mg/m2 intravenously days 1 and 8, for a maximum of six cycles. None of the patients had received prior chemotherapy for metastatic/advanced disease. Fifty-three per cent of patients with bone metastases and 67% of patients without bone metastases had visceral disease. The median age was 70 years for the 15 with bone involvement patients and 73 years for the 21 without bone involvement patients. RESULTS:Twenty-eight patients were fully evaluable for hematological dose-limiting toxicity (DLT), and all patients for other DLTs and for antitumor activity. One DLT with grade 3 venous thrombosis at dose level 2 and two dose-limiting neutropenia events at level 3 occurred in patients without bone involvement. Two dose-limiting neutropenia events were observed at dose level 2 for patients with bone involvement. Thus, the recommended dose was defined at level 1 (capecitabine 1000 mg/m2 days 1-14 and vinorelbine 20 mg/m2 days 1 and 8) for patients with bone involvement. For patients without bone involvement, the recommended dose was at level 2 (capecitabine 1250 mg/m2 days 1-14 and vinorelbine 20 mg/m2 days 1 and 8). For patients without bone involvement the overall response rate was 48% and the time to progression (TTP) was 4.5 months [95% confidence interval (CI) 3.3-6.9]. For patients with bone involvement the overall response rate was 53% and TTP was 5.3 months (95% CI 2.7-7.8). CONCLUSIONS:This regimen of capecitabine and vinorelbine is well tolerated and effective in elderly patients with metastatic breast cancer. Toxicity was mainly hematological and was observed at a lower dose in patients with bone involvement. A phase II study with the two different dose levels for elderly patients with and without bone involvement is currently being conducted. 10.1093/annonc/mdh467
    Gemcitabine in combination with vinorelbine for heavily pretreated advanced breast cancer. Gennatas Constantine,Michalaki Vasiliki,Mouratidou Despina,Tsavaris Nikolaos,Andreadis Charalambos,Psychogios John,Poulakaki Nikiforita Anticancer research PURPOSE:To evaluate the activity and toxicity of gemcitabine and vinorelbine in patients with metastatic breast cancer (MBC), previously treated with anthracyclines alone or with taxanes. PATIENTS AND METHODS:A total of 86 pretreated patients with MBC (median age 62 years), entered the study. Thirty-six patients had been pretreated with anthracyclines and 8 were resistant. The combination of gemcitabine (1000 mg/m2) and vinorelbine (25 mg/m2) was administered on days 1 and 8 every 3 weeks, for a total of 6 cycles. RESULTS:A total of 344 cycles of chemotherapy were administered (median 4 cycles per patient). Partial responses were observed in 31 patients (36.0%; 95% CI: 23-56). The median duration of response was 7 months (range 3-11 months) and the median overall survival was 14 months (range 6-21). The scheme was well tolerated. CONCLUSION:The combination of vinorelbine and gemcitabine is an active scheme in pretreated MBC, demonstrating an acceptable toxicity profile, and may well represent a valuable therapeutic choice after anthracycline/taxane regimens.
    Gemcitabine and oral vinorelbine as salvage treatment in patients with advanced anthracycline- and taxane-pretreated breast cancer. Ardavanis A,Kountourakis P,Maliou S,Vassilakopoulou M,Basioukas S,Kyriakou F,Koumna S,Rigatos G Anticancer research BACKGROUND:Despite progress achieved with new chemotherapeutic and endocrine agents, advanced breast cancer (ABC) remains a disease with poor prognosis. We sought to determine the efficacy of gemcitabine (GC) and oral vinorelbine (VB) in heavily preatreated ABC. PATIENTS AND METHODS:Patients previously treated with anthracyclines and taxanes in the metastatic setting with progressive disease were eligible. Treatment consisted of VB (60 mg/m2, orally) and GC (1000 mg/m2, intravenous infusion), every two weeks of a 28- day cycle. RESULTS:Thirty-one patients with ABC were enrolled. Toxicity was acceptable, mainly haematological. Three and 8 patients achieved a complete (9.6%) and partial (25.8%) response, respectively; ten patients (32.2%) had stable disease. Median time-to-progression was 5.3 months, while in responders 8.6 months. Median overall survival was 14 months. CONCLUSION:Oral VB and GC is an active and well-tolerated combination in anthracycline/taxane-pretreated ABC, representing an interesting option in this poor prognosis group of patients.
    Biweekly gemcitabine plus vinorelbine in first-line metastatic breast cancer: efficacy and correlation with HER2 extracellular domain. Colomer R,Llombart-Cussac A,Tusquets I,Rifà J,Mayordomo J I,Ojeda B,Ciruelos E,Hornedo J,Vicente D,Cortés-Funes H Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico Purpose. To assess the toxicity and efficacy of biweekly gemcitabine plus vinorelbine in first-line advanced breast cancer, and to establish whether circulating HER2 ECD levels correlate with the efficacy of the combination. Patients and methods. 52 patients were treated with gemcitabine 2500 mg/m(2) plus vinorelbine 30 mg/m(2), both on day 1 of 14-day cycles, for a maximum of 10 cycles. Baseline serum levels of HER2 ECD were assessed with an ELISA. Results. All patients were evaluable for toxicity, and 50 for efficacy. Overall toxicity was moderate. Grade 3 neutropenia occurred in 35% of patients and grade 4 in 19%. Other grade 3 toxicities were observed in less than 6%. There was one episode of febrile neutropenia, and one death after cycle three. Overall response rate was 52% (95% CI: 38% to 66%), with 2 patients achieving a CR (4%). Response rate did not correlate with HER2 ECD, with 50% of HER2 ECD positive patients responding, vs 48.5% of the HER2 ECD negative. Median overall survival was 24.6 months. Conclusion. Gemcitabine plus vinorelbine, given as an every-two-week schedule, is an active regimen in advanced breast carcinoma. This combination can be an option when anthracyclines and taxanes are not preferred. HER2 ECD has no predictive value in this non-taxane combination. 10.1007/s12094-006-0153-2
    Which benefit from adding gemcitabine to vinorelbine in elderly (>or=70 years) women with metastatic breast cancer? Early interruption of a phase II study. Basso U,Fratino L,Brunello A,Lumachi F,De Salvo G L,Lonardi S,Ghiotto C,Koussis H,Pasetto L M,Monfardini S Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Since vinorelbine and gemcitabine are both active in breast cancer with moderate toxicity, in 2002 we started a phase II trial with a combination regimen in elderly patients. PATIENTS AND METHODS:To evaluate complete plus partial response rates and toxicity of first-line vinorelbine 25 mg/m2 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 3 weeks, in women>or=70 years with advanced breast cancer and measurable lesions. All patients underwent multidimensional geriatric assessment before enrollment. A two-step design was applied, and the trial would be completed if an overall response rate>or=30% was obtained with a grade 3-grade 4 (G3-G4) toxicity rate<or=25% (excluding neutropenia) in the first step. RESULTS:Twelve eligible patients had a median age of 74 years. At MGA, eight patients were fit, three vulnerable, one frail due to major depression; only two patients had G3 comorbidities according to Cumulative Illness Rating Scale-Geriatric. Seventy-five percent of patients had visceral disease. We obtained only one partial remission (11.1%) and six stabilizations of disease in nine assessable patients, with a time to progression of 3 months. Three patients (25%) experienced G3 neutropenia, and three patients (25%) developed G3 anemia (one patient) and G3 gastrointestinal toxicity (two patients). CONCLUSIONS:The promising response rates obtained with this combination by other authors could not be confirmed in our small cohort of older women with breast cancer, therefore the trial was prematurely terminated. We do not recommend the co-administration of gemcitabine to vinorelbine in women>or=70 years outside the setting of controlled clinical trials. 10.1093/annonc/mdl338
    [A phase-I clinical study of a combination therapy of vinorelbine and capecitabine in patients with advanced/recurrent breast cancer]. Sano Muneaki,Tokuda Yutaka,Noguchi Shinzaburo,Aogi Kenjiro,Saeki Toshiaki,Tabei Toshio,Hatake Kiyohiko,Fujii Hirofumi Gan to kagaku ryoho. Cancer & chemotherapy A phase-I clinical study of a combination therapy of vinorelbine and capecitabine was conducted in anthracycline- and taxane-pretreated patients with advanced/recurrent breast cancer. The objectives of this study in four medical institutions were to evaluate DLT (Dose Limiting Toxicity) and safety as primary endpoints, and tumor response and pharmacokinetics of vinorelbine as secondary endpoints. One 3-week course of treatment consisted of intravenous vinorelbine on Days 1 and 8 and oral capecitabine on Days 1 to 14, followed by a one-week rest. Vinorelbine was given at 20 mg/m(2) (Level 1) and 25 mg/m(2) (Level 2), and capecitabine was given at 1,650 mg/m(2)/day (in two divided doses, Levels 1 - 2). As the administration at each dose level in 3 patients did not cause DLT, 6 patients were additionally treated with vinorelbine at 25 mg/m(2) and capecitabine at 1,650 mg/m(2)/day (in two divided doses) to confirm safety. The major toxicities were bone marrow depression and gastrointestinal symptoms. In particular, the incidences of grade 3 or greater neutropenia (11 patients) and leukemia (10 patients) were high. They were reversible, however, and not severe enough to discontinue treatment. The response rate was 25.0% (3 PR/12). The combination with capecitabine did not affect the plasma pharmacokinetics of vinorelbine.
    A clinical phase II study of cisplatinum and vinorelbine (PVn) in advanced breast carcinoma (ABC). Shamseddine Ali,Khalifeh Mohammed,Chehal Aref,Saliba Teddy,Mourad Yasser Abou,Taher Ali,Jalloul Rahif,Bitar Nizar,Dandashi Azzam,Abbas Jaber,Geara Fady B American journal of clinical oncology OBJECTIVES:The effectiveness of cisplatinum and vinorelbine (PVn) as a salvage regimen in patients with metastatic breast cancer was reported in previous studies. This report is a pilot study assessing the antitumor efficacy and safety of this regimen as first line therapy for advanced breast cancer patients. METHODS:Thirty-five patients were enrolled: 22 with metastatic breast carcinoma and 13 with locally advanced breast carcinoma (stage III). A total of 4 cycles of PVn were planned. After the 4th cycle, patients with metastatic breast cancer received vinorelbine biweekly until disease progression or for a total of 12 cycles, whereas those with locally advanced breast cancer who showed complete or partial response underwent curative surgery. RESULTS:The overall response rate of our whole population was 74.29%. For the metastatic breast cancer group, the overall response rate was 64%, with a median survival of 19 months (range 2-36). For the locally advanced breast cancer group, the overall response rate was 92.3% with a median time to disease progression of 26 months (range 25-27). Toxicity was acceptable, and no treatment-related mortality was encountered. CONCLUSIONS:PVn is effective as first line treatment of advanced breast cancer with overall response rate of 64% in metastatic breast cancer and 92.3% in locally advanced breast cancer, and acceptable toxicity.
    Late phase II clinical study of vinorelbine monotherapy in advanced or recurrent breast cancer previously treated with anthracyclines and taxanes. Toi Masakazu,Saeki Toshiaki,Aogi Kenjiro,Sano Muneaki,Hatake Kiyohiko,Asaga Taro,Tokuda Yutaka,Mitsuyama Shoshu,Kimura Morihiko,Kobayashi Tadashi,Tamura Motoshi,Tabei Toshio,Shin Eisei,Nishimura Reiki,Ohno Shinji,Takashima Shigemitsu Japanese journal of clinical oncology BACKGROUND:At present, it is one of the most important issues for the treatment of breast cancer to develop the standard therapy for patients previously treated with anthracyclines and taxanes. With the objective of determining the usefulness of vinorelbine monotherapy in patients with advanced or recurrent breast cancer after standard therapy, we evaluated the efficacy and safety of vinorelbine in patients previously treated with anthracyclines and taxanes. METHODS:Vinorelbine was administered at a dose level of 25 mg/m(2) intravenously on days 1 and 8 of a 3 week cycle. Patients were given three or more cycles in the absence of tumor progression. A maximum of nine cycles were administered. RESULTS:The response rate in 50 evaluable patients was 20.0% (10 out of 50; 95% confidence interval, 10.0-33.7%). Responders plus those who had minor response (MR) or no change (NC) accounted for 58.0% [10 partial responses (PRs) + one MR + 18 NCs out of 50]. The Kaplan-Meier estimate (50% point) of time to progression (TTP) was 115.0 days. The response rate in the visceral organs was 17.3% (nine PRs out of 52). The major toxicity was myelosuppression, which was reversible and did not require discontinuation of treatment. CONCLUSION:The results of this study show that vinorelbine monotherapy is useful in patients with advanced or recurrent breast cancer previously exposed to both anthracyclines and taxanes. 10.1093/jjco/hyi090
    Primary chemotherapy with epirubicin and vinorelbine in women with locally advanced breast cancer. Nisticò Cecilia,De Matteis Andrea,Rossi Emanuela,Carnino Flavio,Valenza Roberto,Agostara Biagio,Bria Emilio,Farris Antonio,Cremonesi Marco,D'Ottavio Anna Maria,Vaccaro Angela,Garufi Carlo,Giunta Salvatore,Botti Claudio,Perrone Francesco,Terzoli Edmondo Anticancer research BACKGROUND:To assess the activity and toxicity of primary chemotherapy with epirubicin (60 mg/m2 every other week) and vinorelbine (25 mg/m2, weekly) plus granulocyte colony-stimulating factor (G-CSF) for 12 weeks, in patients with locally advanced breast cancer in a multicenter setting. PATIENTS AND METHODS:Patients with stage IIIA or IIIB breast cancer, not older than 70, were eligible. A two-stage phase II design was applied. Response was assessed clinically, instrumentally and pathologically. RESULTS:Out of 48 enrolled patients, 87.5% received all planned cycles, with a median dose-intensity of 30 mg/m2/week for epirubicin and 23.8 mg/m2/week for vinorelbine. A clinical or instrumental objective response was reached in 42 patients (87.5%, exact 95% CI: 74.7-95.3); significant downstaging was reached in all but one patient; 6 cases had a pathological complete response in the breast, and 2 cases in the lymph nodes too (pathological complete response rate 4.2%, exact 95% CI: 0.5-14.2); a further 2 patients had only microscopic cancer foci at pathological examination of the breast. Radiological tests underestimated the treatment effect on the breast. Toxicity was mild, neutropenia being the most frequent (grade 3-4 in 47% of patients), but never complicated with fever or sepsis. Mild constipation (< or =grade 2) occurred in 35% of patients. Moderate to severe asthenia occurred in 12% of 6 patients. No cardiac toxicity was reported. At 3 years, disease-free survival was 68% and overall survival 81%. CONCLUSION:Primary chemotherapy with epirubicin every other week, weekly vinorelbine and G-CSF support is highly active and well tolerated in patients with locally advanced breast cancer.
    Oral vinorelbine plus capecitabine (oral vincap) combination in patients with advanced breast cancer (ABC). A phase II study of the GOIM (Gruppo Oncologico dell'Italia Meridionale). Lorusso V,Spada M,Giampaglia M,Misino A,Calabrese R,Latorre A,Monticelli G,Guida M,Sambiasi D,Colucci G, Annals of oncology : official journal of the European Society for Medical Oncology BACKGROUND:Vinorelbine i.v. and capecitabine are two of the most effective single agents in previously treated advanced breast cancer (ABC). A number of studies have been reported with the combination of these agents. Actually, the availability of oral formulation for vinorelbine allows a full oral combination of the two agents. The aim of this study was to evaluate the activity and toxicity of this novel combination. PATIENTS AND METHODS:Thirty-eight advanced breast cancer patients refractory to anthracyclines and taxanes were included in this study. Treatment consisted of vinorelbine 60 mg/m(2) (days 1 + 8), and capecitabine 2000 mg/m(2) (days 2-7 and 9-16) every 3 weeks. RESULTS:A total of 228 courses were given with a mean of three cycles/patient (range 1-12). Five patients (13.1%) had no toxicity at all. Hematologic side-effects were: neutropenia grade 2-3 in seven patients (18.9%) and grade 4 in one patient (2.7%), anemia grade 1 in 11 patients (29.7%), grade 2-3 in five patients (13.5%), thrombocytopenia grade 1 in six patients (16.2%) and grade 3 in one patient (2.7%). Non-hematologic side-effects were: fatigue grade 1 in five patients (13.5%), hand-foot syndrome grade 1 in two patients (5.4%) and grade 2 in two patients (5.4%), nausea/vomiting grade 1 in two patients (5.4%), grade 2 in three patients (8.1%) and grade 3 in one patient (2.7%), constipation grade 1 in two patients (5.4%), peripheral neurotoxicity grade 1 in three patients (8.1%) and grade 2 in one patient (2.7%), gastric pain grade 1 in two patients (5.4%), stomatitis grade 1 in three patients (8.1%) and grade 2 in one patient (2.7%). Out of 38 patients assessable, we observed two (5.4%) CR, 13 (34 %) PR, 14 (37.8%) SD and nine (26.3%) PD. The median time to progression was 4.5 months (range 1-18 months), the median response duration was 7 months (range 2-18 months) and the median survival duration was 10 months (range 2-26+). CONCLUSIONS:The oral vincap should be considered as an alternative to single agent capecitabine or vinorelbine in ABC refractory to antra-taxane combination. 10.1093/annonc/mdl942
    Sequential vinorelbine-capecitabine followed by docetaxel in advanced breast cancer: long-term results of a pilot phase II trial. Ghosn Marwan,Kattan Joseph,Farhat Fadi,Younes Fariha,Nasr Fadi,Moukadem Walid,Gasmi Jamal,Chahine Georges, Cancer chemotherapy and pharmacology PURPOSE:To evaluate the response rate of the combination of capecitabine (C) and vinorelbine (V) followed by Docetaxel (D) in the 1st line treatment of advanced and metastatic breast cancer patients. PATIENTS AND METHODS:Patients with measurable disease and no prior chemotherapy in advanced disease were eligible. Pts received V 25 mg/m(2) on day 1 and 8 in combination with C 825 mg/m(2) twice a day from day 1 to 14 every 3 weeks for four cycles followed by 12 consecutive weeks of D 25 mg/m(2)/w. RESULTS:Between March 2002 and November 2003, 40 patients were enrolled. Median age was 57 years. Of patients, 77.5% of pts had visceral involvement and 32.5% had more than two metastatic sites. In the adjuvant setting, 62.5% received anthracycline and 10% Taxanes. In the intent-to-treat population, an overall objective response was observed in 25 patients (62.5, 95% CI, 45.8-77.27) and stable disease in 5 (12.5%). Median time till progression (TTP) was 12.3 months (range 1.5-48; 95% CI, 10.05-14.54). The median survival was 35.7 months (range 2-47). Reported grade 3-4 toxicities under Navcap were neutropenia (4 pts), anemia (1 pt), thrombopenia (1 pt) and febrile neutropenia (3 pts). Reported grade 3-4 toxicities under weekly Docetaxel were neutropenia (1 pt), thrombopenia (2 pts), leucopenia (1 pt) and anemia (1 pt). CONCLUSION:The sequential use of Navcap followed by weekly Docetaxel demonstrated an interesting efficacy with a prolonged TTP and OS and warrants further evaluation. 10.1007/s00280-007-0565-x
    A phase II trial of oral vinorelbine and capecitabine in anthracycline pretreated patients with metastatic breast cancer. Finek Jindrich,Holubec Lubos,Svoboda Tomas,Sefrhansova Lucie,Pavlikova Ivana,Votavova Marie,Sediva Marcela,Filip Stanislav,Kozevnikova Renata,Kormunda Stanislav Anticancer research BACKGROUND:Optimal chemotherapy (CT) for advanced breast treatment should be effective, well tolerated and convenient. In this study the efficacy and safety of the fully oral combination of oral vinorelbine (Navelbine Oral) plus capecitabine (Xeloda) in metastatic breast cancer (MBC) patients pretreated with anthracycline, was evaluated. PATIENTS AND METHODS:In this phase II multicenter study, this combination CT was given as a first- or second-line therapy for MBC. The treatment schedule was: oral vinorelbine 60 mg/m2 day 1 and day 8 plus capecitabine 1,000 mg/m2 twice daily from day 1 to day 14, every 21 days. RESULTS:One hundred and fifteen patients were included in this trial. The median age was 58 years (range: 40-75). All the patients had received prior anthracycline-based chemotherapy. The combination was well tolerated, with, in particular, only 0.8% of patients presenting with febrile neutropenia. In the intention-to-treat (ITT) population, an objective response was achieved in 65 patients (56.5%). A complete response was achieved in 22 patients (19.1%); partial response in 43 patients (37.4%); stable disease in 36 patients (31.3%), and progressive disease was observed in 14 patients (12.2%). After a median follow-up of 10.0 months, the median progression-free survival (PFS) was 10.5 months and the median survival was 17.5 months. CONCLUSION:Oral vinorelbine-capecitabine shows very promising activity and low toxicity in MBC treatment, with high compliance of the patients.
    Capecitabine and vinorelbine as first-line treatment in elderly patients (> or =65 years) with metastatic breast cancer. A phase II trial (SAKK 25/99). Hess D,Koberle D,Thurlimann B,Pagani O,Schonenberger A,Mattmann S,Rochlitz C,Rauch D,Schuller J C,Ballabeni P,Ribi K, Oncology BACKGROUND:We evaluated previously established regimens of capecitabine plus vinorelbine in older patients with advanced breast cancer stratified for presence versus absence of bone metastases. PATIENTS AND METHODS:Patients > or =65 years who had received no prior chemotherapy for advanced breast cancer received up to six 21-day cycles of vinorelbine 20 mg/m(2) i.v. on days 1 + 8 with oral capecitabine on days 1-14 (1,000 vs. 1,250 mg/m(2) daily in patients with vs. without bone involvement). RESULTS:Median age was 72 years in patients with bone metastases (n = 47) and 75 years in patients without bone metastases (n = 23). Response rates were 43% (95% confidence interval, CI, 28.3-58.8) and 57% (95% CI = 34.5-76.8), respectively. Median time to progression was 4.3 (95% CI = 3.5-6.0 months) and 7.0 months (CI = 4.1-8.3), respectively. Neutropenia was the most common toxicity, with grade 3/4 occurring in 43 and 39%, respectively. Pulmonary embolism was seen in 5 and grade 3 thrombosis in 3 patients. Other toxicities were mild to moderate. CONCLUSIONS:These regimens of capecitabine and vinorelbine are active and well tolerated in patients with advanced breast cancer > or =65 years. Response rates were comparable to published results. The lower capecitabine doses appeared appropriate given the advanced age, bone involvement and prior radiotherapy. 10.1159/000127414
    Phase II study of oral vinorelbine in combination with capecitabine as second line chemotherapy in metastatic breast cancer patients previously treated with anthracyclines and taxanes. Jones Alison,O'Brien Mary,Sommer Harald,Nowara Elzbieta,Welt Anja,Pienkowski Tadeusz,Rolski Janusz,Pham My-Linh,Perraud Kevin,Trillet-Lenoir Véronique Cancer chemotherapy and pharmacology PURPOSE:Effective treatment options for patients with metastatic breast cancer (MBC) resistant/refractory to anthracyclines and/or taxanes are limited. Intravenous and oral combination of vinorelbine (VRL) and capecitabine were shown to be feasible and effective in first-line MBC. In order to evaluate the activity of the combination of an all oral regimen in a more advanced setting, we investigated a regimen combining oral VRL and capecitabine in a phase II study as second-line chemotherapy of MBC patients previously treated with anthracyclines and taxanes. PATIENTS AND METHODS:Forty patients (median age 52 years) with MBC received the combination of oral VRL 60 mg/m(2) on days 1, 8 and 15 plus capecitabine 1,000 mg/m(2) bid given from day 1 to day 14 in an open-label, international, multicentre, phase II study. Cycles were repeated every 3 weeks. The primary endpoint was response rate (RR) evaluated by an independent panel review. Secondary objectives included safety, duration of response, progression-free survival, overall survival and quality of life. RESULTS:All the patients had received prior chemotherapy with anthracyclines and taxanes, 75% were refractory/resistant to anthracycline and/or taxane, 72.5% presented with visceral involvement and the last prior chemotherapy for 87.5% of the patients was for advanced disease setting. The median number of administered cycles per patient was 4 (range 1-31). Eight responses were documented and validated by an independent panel review, yielding RRs of 20% [95% CI: 9-35.6] in the intent-to-treat (treated) population and 23.5% [95% CI: 10.7-41.2] in the 34 evaluable patients. Median progression-free survival and median overall survival were 3.4 months [95% CI: 2.3-5.5] and 11.3 months [95% CI: 8.1-16.4], respectively. The principal toxicities were anaemia, neutropenia (rarely complicated; only one patient experienced febrile neutropenia), fatigue and gastrointestinal toxicities with very few grade 3-4 non-haematological toxicities. CONCLUSIONS:In second-line treatment of MBC patients previously treated with anthracyclines and taxanes, oral VRL plus capecitabine is a safe regimen with an efficacy comparable to the other available combination regimens used in this heavily and resistant/refractory (75% of patients) pre-treated patients' population. Moreover, this well-tolerated combination offers the advantages of an all oral regimen. 10.1007/s00280-009-1081-y
    Capecitabine/vinorelbine: an effective and well-tolerated regimen for women with pretreated advanced-stage breast cancer. Nolè Franco,Catania Chiara,Munzone Elisabetta,Rocca Andrea,Verri Elena,Sanna Giuseppina,Ascione Gilda,Adamoli Laura,Zampino Maria G,Minchella Ida,Goldhirsch Aron Clinical breast cancer BACKGROUND:The combination of capecitabine and vinorelbine is a potentially valuable treatment regimen for patients with advanced-stage breast cancer. The drugs are easy to administer and do not cause significant alopecia. In order to identify the spectrum of toxicity of a regimen containing 2 drugs, we conducted an extended phase I study aimed at defining maximum tolerated doses, recommended doses, safety, and efficacy in patients with pretreated advanced-stage breast cancer. PATIENTS AND METHODS:Forty-nine patients with advanced-stage breast cancer were treated with escalating doses of oral capecitabine from 500 mg/m2 to 1375 mg/m2 twice daily on days 1-14 and escalating doses of vinorelbine from 12.5 mg/m2 to 25 mg/m2 intravenously (I.V.) on days 1 and 3 every 3 weeks. Almost all patients (90%) had received >or= 3 previous treatments for metastatic disease (anthracyclines, 76%; 5-flourouracil, 76%; taxanes, 29%). RESULTS:Dose level 9 (capecitabine 1250 mg/m2 twice daily on days 1-14 and vinorelbine 22.5 mg/m2 I.V. on days 1 and 3) was identified as the maximum tolerated dose. The most frequent clinical adverse events were nausea (78%), asthenia (59%), constipation (51%), mucositis (47%), and hand-foot syndrome (41%). The majority of events were mild to moderate; the only grade 4 clinical adverse events were diarrhea, fever, and thromboembolism, each of which occurred in 1 patient (2%) at dose level 8. Objective confirmed responses were observed in 18 patients (37%), including 1 complete response (2%) and 17 partial responses (35%). Disease was stable in an additional 10 patients (20%), with a median duration of 6.3 months (range, 4-24 months). CONCLUSION:The combination of the 2 drugs is very well tolerated and effective, especially considering the previous exposure to chemotherapy. The recommended dose for further phase II studies should be capecitabine 1250 mg/m2 twice daily on days 1-14 and vinorelbine 22.5 mg/m2 I.V. on days 1 and 3. 10.3816/CBC.2006.n.005
    A phase I study of an all-oral combination of vinorelbine/capecitabine in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes. Kellokumpu-Lehtinen Pirkko-Liisa,Sunela Kaisa,Lehtinen Ilari,Joensuu Heikki,Sjöström-Mattson Johanna, Clinical breast cancer BACKGROUND:Few overlapping toxicities and oral formulations make capecitabine plus oral vinorelbine an attractive new combination for treating patients with breast cancer. An all-oral regimen minimizes inconvenience for the patient and saves medical resources. PATIENTS AND METHODS:To determine the recommended dose for this all-oral combination, we conducted a phase I study in 21 patients with metastatic breast cancer after failure of previous chemotherapy with anthracylines and/or taxanes for advanced disease. Capecitabine 1000 mg/m2 twice daily was given on days 2-7 and 9-14. Vinorelbine was administered at escalating doses of 40-80 mg/m2 on days 1 and 8 every 3 weeks. Dose escalation of vinorelbine was performed in cohorts of 3 patients, but the dose of vinorelbine could also be increased to the next level in the same patient after 3 cycles if there were no dose-limiting toxicities. In total, 173 cycles were administered (median, 8 cycles; range 1-21+ cycles). RESULTS:Treatment was well tolerated: there were no grade 4 toxicities, and the only grade 3 toxicities in > 1 cycle were hand-foot syndrome and neutropenia (2% of cycles each). The maximum tolerated dose could not be determined using predefined criteria. However, in this heavily pretreated patient population, intrapatient vinorelbine dose escalation > 60 mg/m2 was rarely achieved. Thus, we considered vinorelbine 60 mg/m2 to offer the best dose level-toxicity ratio. At this dose, grade 3 toxicities occurred in only 7% of the 58 cycles administered. Among 19 evaluable patients, 7 exhibited response or stable disease lasting > 6 months, giving a clinical benefit rate of 37%. Duration of response in the 2 responding patients was 5 months and > 16 months. CONCLUSION:The all-oral combination of capecitabine/vinorelbine is well tolerated and active in heavily pretreated patients. Oral vinorelbine 60 mg/m2 is recommended in combination with capecitabine 1000 mg/m2 twice daily for further evaluation. 10.3816/cbc.2006.n.057
    Efficacy and toxicity of vinorelbine with doxorubicin/cyclophosphamide combination chemotherapy in a phase I-II study for advanced or recurrent breast cancer patients. Saeki Toshiaki,Takashima Shigemitsu,Ogita Masami,Tabei Toshio,Adachi Isamu,Tamura Kazuo,Takatsuka Yuichi,Kanda Kazuhiro Breast cancer (Tokyo, Japan) BACKGROUND:To evaluate the efficacy and toxicity of vinorelbine (VNB) with doxorubicin/cyclophosphamide (AC) combination chemotherapy, a phase I-II study was carried out in patients with advanced or recurrent breast cancer. METHODS:The phase I part of this study was carried out to determine the treatment schedule and acceptable dose of VNB for the phase II study. In phase I, VNB was initially given as a short infusion on days 1, 8 and 15, every 4 weeks. The initial dose of vinorelbine was 15 mg/m2. In the AC regimen, 20 mg/m2 of doxorubicin (ADM) was given intravenously (i.v.) on days 1 and 8, and 100 mg/body of cyclophosphamide (CPA) was administered orally from days 1 to 14. Subsequently, a phase II study was carried out at the maximum acceptable dose (MAD). RESULTS:Twenty-three patients were entered into this study. In patients receiving VNB at a dose of 15 mg/m2, neutropenia (> or = grade 3) frequently occurred on day 15. The treatment schedule of this study was therefore changed to VNB given i.v. on days 1 and 8 with AC combination chemotherapy. In this treatment schedule, grade 4 neutropenia lasting for more than 4 days occurred in patients given VNB at a dose of 20 mg/m2 with AC more frequently than in those given 15 mg/m2 of VNB. Therefore, the MAD of VNB was determined to be 20 mg/m2 in this regimen. At this recommended dose, there were 1 complete (CR) and 8 partial responses (PRs) in 15 patients, with an overall response rate of 60.0%. No treatment-related death occurred. CONCLUSIONS:These data indicate that VNB plus AC combination chemotherapy was effective and well tolerated for breast cancer patients. A randomized trial of VNB plus AC vs. AC combination chemotherapy may be required to ascertain the benefit of this regimen for advanced or recurrent breast cancer patients. 10.2325/jbcs.13.159
    Neoadjuvant sequential epirubicin and docetaxel followed by surgery-radiotherapy and post-operative docetaxel or gemcitabine/vinorelbine combination based on primary response: a multimodality approach for locally advanced breast cancer. Kountourakis Panteleimon,Missitzis Ioannis,Doufexis Dimitrios,Zobolas Vassileios,Pissakas Georgios,Arnogiannaki Niki,Maliou Savoula,Sotiropoulou Anastasia,Ardavanis Alexandros Journal of cancer research and clinical oncology BACKGROUND:Locally advanced breast cancer (LABC) remains a major clinical issue despite progress achieved in recent years. Herein, we present the mature results of a multimodality treatment program tailoring epirubicin (EPI), docetaxel (DOC) and gemcitabine-vinorelbine (GEV) peri-operatively in LABC. PATIENTS AND METHODS:Stage III, Eastern Cooperative Oncology Group-Performance status ≤2 patients were eligible. A biopsy documentation had to be performed before the start of chemotherapy (CT). Treatment consisted of four EPI (100 mg/m(2), d1q2w) followed by three DOC (100 mg/m(2), d1q3w); surgery 3-4 weeks from CT completion, followed by radiation therapy (RT) and CT according to response; partial or complete (PR/CR):DOC, no change or progressive disease (NC/PD):GEV. Primary endpoints were: (a) response and conversion to operability/conservative surgery and (b) overall survival (OS) and time to recurrence (TTR). RESULTS:Fifty-six women, aged 32-75 (median 52 years), 24 IIIA and 32 IIIB were enrolled; 53 patients completed the entire program. Toxicity was acceptable and no treatment-related death was observed. EFFICACY:clinical response rate (RR) 71.4% (40 patients); clinical complete response rate 33.9% (19 patients). Pathological response rate (RR) 67.8% (38 patients); pathological complete response rate 21.4% (12 patients). 33 (58.9%) and 19 (33.9%) patients, respectively, had radical and conservative operations without increased morbidity. After a median follow-up of 62 months, median OS has not yet been reached, while median TTR was 42 months. OS was longer in patients with clinical (p = 0.004) and pathological response (p = 0.002), RT (p < 0.0001) and post-operative DOC (p = 0.038). TTR was favorably affected by pR (p < 0.0001), RT (p < 0.0004) and post-operative DOC (p = 0.005). Pre-operative CT seemed to be equally active throughout all subgroups according to histology, ER/PR and HER2 status. CONCLUSION:The treatment program of the present study allowed for the completion of an effective therapy at the cost of acceptable toxicity. The results of this study suggest a central role of CT for LABC and the value of eventually dose-dense, EPI- and DOC-based CT in a large proportion of LABC patients, regardless of biological tumor profile. Furthermore, tumor response (cR, pR) is an important surrogate for patients survival and further therapy management. 10.1007/s00432-010-0878-8
    On and off metronomic oral vinorelbine in elderly women with advanced breast cancer. De Iuliis Francesca,Salerno Gerardo,Taglieri Ludovica,Lanza Rosina,Scarpa Susanna Tumori BACKGROUND:Elderly patients with metastatic breast cancer (MBC) have more problems receiving chemotherapy than younger patients, especially with the presence of multiple comorbidities, adverse drug events and functional decline. Low-dose oral administration of cytotoxic agents such as vinorelbine, a semisynthetic vinca alkaloid that interferes with microtubule assembly, leading to arrest of cell division, is usually effective and well tolerated. METHODS:From February 2010 to February 2014, 32 patients with MBC, median age 76 years (range 69-83) were treated with oral vinorelbine 30 mg (total dose), one day on and one day off, until disease progression or unacceptable toxicity levels were reported. Toxicity, quality of life and clinical benefit were evaluated. Matched t-tests were conducted to discern whether quality-of-life indicator (p&lt;0.05 was considered significant) differed before and 6 months after treatment. Statistical analysis was performed using Graph Pad Prism 5.0 (GraphPad Software Inc., San Diego, CA, USA). RESULTS:No grade 3 and 4 adverse events were reported. A clinical benefit of 50% was found in our cohort. On and off metronomic vinorelbine oral administration resulted in good tolerability and safe profile in our selected elderly population, and improved patient adherence to therapy. CONCLUSIONS:The present study demonstrated that metronomic vinorelbine might be a potential treatment in elderly patients by reducing adverse effects and increasing quality of life, setting the stage for future extensive clinical trials. 10.5301/tj.5000207
    Capecitabine and bevacizumab with or without vinorelbine in first-line treatment of HER2/neu-negative metastatic or locally advanced breast cancer: final efficacy and safety data of the randomised, open-label superiority phase 3 CARIN trial. Welt A,Marschner N,Lerchenmueller C,Decker T,Steffens C-C,Koehler A,Depenbusch R,Busies S,Hegewisch-Becker S Breast cancer research and treatment The study was designed to evaluate efficacy and superiority of capecitabine/bevacizumab + vinorelbine (CAP/BEV/VIN) compared to CAP/BEV alone. Main purpose was to introduce a taxane-/anthracycline-free first-line treatment in advanced breast cancer (ABC), in order to avoid long-term toxicities. In this open-label, superiority, phase 3 trial, patients with HER2-negative ABC were randomized 1:1 to receive either oral CAP at 1000 mg/m(2) [twice daily, days 1-14, q3w] plus intravenous BEV at 15 mg/kg [day 1, q3w] (arm A) or in addition to this protocol intravenous VIN at 25 mg/m(2) [days 1 + 8, q3w] (arm B) until disease progression, unacceptable toxicity or withdrawal of consent. Between 26 February 2009 and 26 October 2012, we randomised 600 patients (arm A N = 300; arm B N = 300) from 57 German outpatient-centres and 2 university hospitals. Median progression-free survival (PFS) (primary endpoint) was not improved with VIN (CAP/BEV, 8.8 months; CAP/BEV/VIN, 9.6 months; HR 0.84 [95 % CI 0.70-1.01], P = 0.058). Median overall survival (OS) (secondary endpoint) was 25.1 and 27.2 months for CAP/BEV and CAP/BEV/VIN, respectively, average HR 0.85 [95 % CI 0.70-1.03], P = 0.104). The 1- and 2-year OS rates appeared to be similar (78.0 and 77.0 %; 53.0 and 54.0 %). Toxicity profiles were generally mild and manageable. Adverse events occurred more frequently in arm B. Regarding the balance between clinical efficacy (PFS, OS) and toxicity, the CAP/BEV combination provides a favourable treatment option in first-line ABC avoiding taxane- and/or anthracycline-induced long-term toxicity. Superiority of CAP/BEV/VIN was not met, and side effects were even enhanced. Nevertheless, no safety issues occurred. 10.1007/s10549-016-3727-x
    Capecitabine combined with docetaxel versus vinorelbine followed by capecitabine maintenance medication for first-line treatment of patients with advanced breast cancer: Phase 3 randomized trial. Wang Jiayu,Xu Binghe,Yuan Peng,Ma Fei,Li Qing,Zhang Pin,Cai Ruigang,Fan Ying,Luo Yang,Li Qiao Cancer BACKGROUND:In this prospective study, progression-free survival (PFS) and the safety profiles of docetaxel/capecitabine (TX) and vinorelbine/capecitabine (NX) followed by capecitabine maintenance therapy were compared in patients with metastatic breast cancer. METHODS:Patients with advanced metastatic breast cancer were randomly assigned to a TX group (n = 104) and an NX group (n = 102), both of which included capecitabine maintenance medication. The primary endpoint was progression-free survival (PFS). RESULTS:The trial met its primary endpoint and was closed to accrual subsequent to interim analysis. Forty-eight patients in the TX group (46.2%) and 42 patients in the NX group (41.2%) received maintenance medication. The median PFS (8.4 vs 7.1 months; P = .0026; 95% confidence interval, 1.18-2.3; hazard ratio, 1.65), the response duration (7.8 vs 6.6 months; P = .0451), and the median overall survival (OS) (35.3 vs 19.8 months; P = .1349; 95% confidence interval, 0.88-2.47; hazard ratio, 1.48) in the TX group appeared to be longer compared with those in the NX group, although the difference did reach not statistical significance. Patients aged ≥40 years who were postmenopausal and presented with visceral metastases were more likely to benefit from the TX regimen in terms of PFS and OS, whereas positive hormone receptor and human epidermal growth factor receptor 2 status or a history of taxane treatments did not affect differences in PFS and OS between the TX and NX groups. Hand-foot syndrome occurred more frequently in the TX group than in the NX group (47% vs 16.7%; P < .0001), but the frequencies of other minor adverse effects were similar in both groups. CONCLUSIONS:A TX regimen for advanced breast cancer followed by capecitabine maintenance medication led to longer PFS and response duration than an NX regimen, even for patients who had previously received taxane in (neo)adjuvant settings. Cancer 2015. © 2015 American Cancer Society. Cancer 2015;121:3435-43. © 2015 American Cancer Society. 10.1002/cncr.29492
    Vinorelbine Plus Gemcitabine or Cisplatin as First-line Treatment of HER2-negative Advanced Breast Cancer. He Kewen,Wang Xinzhao,Guan Xiyun,Yu Qian,Ma Qinghua,Liu Zhaoyun,Yu Zhiyong Anticancer research AIM:To evaluate the efficacy and toxicity of vinorelbine and gemcitabine (NG) versus vinorelbine and cisplatin (NP) in anthracycline- and taxane-pretreated patients with HER2-negative advanced breast cancer. PATIENTS AND METHODS:Patients were randomly assigned on a 1:1 schedule to receive no more than six cycles of NG or NP. Dosing for the NG group was 25 mg/m vinorelbine and 1,000 mg/m gemcitabine, given on days 1 and 8 every 3 weeks; for the NP group,25 mg/m vinorelbine was given on days 1 and 8, and 75 mg/m cisplatin was given on day 1 every 3 weeks. The primary endpoint was disease control rate (DCR). The secondary endpoints were the progression-free survival (PFS), overall survival (OS) and safety. RESULTS:The full analysis set comprised of 37 patients receiving NG and 37 receiving NP. The DCR was 70.3% with NG and 64.9% with NP (p=0.619). Median PFS were 7 months (95% CI=5.88-8.12) and 6 months (95% CI=5.29-6.71) respectively in NG and NP group [hazard ratio (HR)=1.696; 95% confidence interval (CI)=0.73-3.93; p=0.217)]. Corresponding median OS was 18 (95% CI=10.35-13.65) months and 12 (95% CI=15.83-20.17) months (HR=1.219; 95% CI=0.67-2.23; p=0.521). For adverse events, neutropenia and nausea/vomiting were milder in the NG group than in the NP group (all p<0.05). CONCLUSION:Although no significant differences were observed in terms of DCR, PFS and OS, with milder toxicity, NG appeared to be a more valuable first-line treatment regimen than NP in anthracycline- and taxane-pretreated patients with HER2-negative advanced breast cancer. 10.21873/anticanres.12000
    Randomized phase II study evaluating weekly oral vinorelbine versus weekly paclitaxel in estrogen receptor-positive, HER2-negative patients with advanced breast cancer (NorBreast-231 trial). Aapro Matti,Ruiz-Borrego Manuel,Hegg Roberto,Kukielka-Budny Bozena,Morales Serafin,Cinieri Saverio,Freitas-Junior Ruffo,Garcia-Estevez Laura,Szombara Ewa,Borges Giuliano Santos,Passalacqua Rodolfo,Hervieu Helene,Groc Mélanie,Villanova Gustavo Breast (Edinburgh, Scotland) BACKGROUND:Single-agent paclitaxel and vinorelbine are recommended treatments for advanced breast cancer (ABC) non-responsive to hormone therapy and without visceral crisis. This phase II trial compared first-line oral vinorelbine versus weekly paclitaxel for ABC. METHODS:Eligible female patients had measurable locally recurrent/metastatic estrogen receptor-positive HER2-negative breast cancer and had received prior endocrine therapy (any setting) but no chemotherapy for ABC. Patients were stratified by prior taxane and visceral metastases and randomized to either oral vinorelbine 80 mg/m (first cycle at 60 mg/m, escalated to 80 mg/m in the absence of grade 3/4 toxicity) or intravenous paclitaxel 80 mg/m on days 1, 8, and 15 every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was disease control rate (DCR; confirmed complete or partial response, or stable disease for ≥6 weeks). RESULTS:The 131 randomized patients had received a median of 2 prior endocrine therapies; >70% had prior (neo)adjuvant chemotherapy and 79% visceral metastases. DCR was 75.8% (95% confidence interval: 63.6-85.5%) with vinorelbine and 75.4% (63.1-85.2%) with paclitaxel. The most common grade 3/4 adverse events were neutropenia (52%), fatigue (11%), and vomiting (5%) with vinorelbine, and neutropenia (17%), dyspnea (6%), hypertension (6%), and peripheral sensory neuropathy (5%) with paclitaxel. Grade 2 alopecia occurred in 2% of vinorelbine-treated and 34% of paclitaxel-treated patients. Neither arm showed relevant global health status changes. CONCLUSION:Oral vinorelbine and paclitaxel demonstrated similar DCRs (∼75%). Safety profiles differed and, together with administration route and convenience, may influence treatment choice (EudraCT number, 2012-003530-16). 10.1016/j.breast.2019.01.009
    VicTORia: a randomised phase II study to compare vinorelbine in combination with the mTOR inhibitor everolimus versus vinorelbine monotherapy for second-line chemotherapy in advanced HER2-negative breast cancer. Decker Thomas,Marschner Norbert,Muendlein Axel,Welt Anja,Hagen Volker,Rauh Jaqueline,Schröder Helge,Jaehnig Peter,Potthoff Karin,Lerchenmüller Christian Breast cancer research and treatment PURPOSE:Improving the outcome of patients with HER2-negative metastatic breast cancer experiencing tumour progression following first-line chemotherapy remains an urgent medical need. The purpose of the VicTORia trial was to show superiority of everolimus in combination with vinorelbine versus vinorelbine monotherapy as second-line chemotherapy for patients with advanced HER2 negative breast cancer. METHODS:In this randomised phase II trial, 133 patients were recruited in 32 centres in Germany. Patients were randomised 1:1 to second-line chemotherapy either with vinorelbine plus everolimus (arm1) or vinorelbine alone (arm2). Primary endpoint was progression-free survival (PFS). Secondary endpoints were PFS rate at 6 months, overall survival (OS), overall response rate (ORR) and safety. Baseline PI3 K mutational status was determined in plasma samples. RESULTS:Median progression-free survival was not different between arms (arm1 vs. arm2: 4.01 months, 95% CI 2.40-6.09 vs. 4.08, 95% CI 2.80-5.33). PFS rate at 6 months (arm1 vs. arm2: 39.4%, 95% CI 27.6-50.9% vs. 36.6%, 95% CI 24.6-48.6%), median OS (arm1 vs. arm2: 16.3 months, 95% CI 11.4-19.0 vs. 13.8 months, 95% CI 10.2-19.1) and ORR were not different between arms. Most frequent grade 3/4 adverse events were neutropenia (50% vs. 40%), gastrointestinal toxicities (19.1% vs. 6.1%), and infections (19.1% vs. 7.7%). PI3 K mutational status was neither associated with PFS nor with OS. CONCLUSION:Although well tolerated, the efficacy of everolimus and vinorelbine combination therapy was not superior to vinorelbine monotherapy. There was no correlation between PI3 K mutational status and efficacy. EudracCT No 2011-001024-38, ClinicalTrials.gov No NCT01520103. 10.1007/s10549-019-05280-2