Research on the efficacy of cisplatin and nimotuzumab combined with concurrent chemoradiotherapy on locally advanced cervical cancer.
Cao Ye,Deng Li,Lian Shixian,Jiang Ying
Journal of B.U.ON. : official journal of the Balkan Union of Oncology
PURPOSE:To evaluate the efficacy and safety of cisplatin and nimotuzumab combined with concurrent chemoradiotherapy on locally advanced cervical cancer. METHODS:92 patients with cervical cancer in moderate and advanced stages treated in Shanghai Public Health Clinical Center from January 2014 to January 2017 were selected and divided into two groups with 46 cases in each group. They received cisplatin and nimotuzumab combined with concurrent chemoradiotherapy and cisplatin combined with concurrent chemoradiotherapy, respectively. The clinical efficacy, adverse reactions, overall survival (OS) and progression-free survival (PFS) were compared between the two groups. RESULTS:The general clinical characteristics of patients in both groups were comparable. The effective rate was 87.0% and 67.4%, respectively, in nimotuzumab group and cisplatin group, and the local tumor control and short-term efficacy were superior in the nimotuzumab group compared to those in the cisplatin group (p=0.045). There was no statistically significant difference in the incidence of complications after treatment between the two groups (p>0.05), and nimotuzumab did not increase the incidence and severity of adverse reactions. The 3-year OS rate was 87.0% (40/46) and 69.6% (32/46), respectively, in the two groups (log-rank, p=0.070). The 3-year PFS rate in the nimotuzumab group [73.9% (34/46)] was obviously higher than that in the cisplatin group [50.0% (23/46)] (p=0.042). CONCLUSIONS:Cisplatin and nimotuzumab combined with concurrent chemoradiotherapy is safe and effective in the treatment of locally advanced cervical cancer, both local tumor control and PFS rate are excellent, and the patient's tolerance is good, so it is worth of clinical popularization.
Administration of nimotuzumab combined with cisplatin plus 5-fluorouracil as induction therapy improves treatment response and tolerance in patients with locally advanced nasopharyngeal carcinoma receiving concurrent radiochemotherapy: a multicenter randomized controlled study.
Lu Ying,Chen Dagui,Liang Jinhui,Gao Jianquan,Luo Zhanxiong,Wang Rensheng,Liu Wenqi,Huang Changjie,Ning Xuejian,Liu Meilian,Huang Haixin
BMC cancer
BACKGROUND:Nimotuzumab (NTZ) is an anti-EGFR monoclonal antibody. However,the effect of targeted drugs combined with induction therapy in locally advanced nasopharyngeal carcinoma remains unclear. The aim of this study is to investigate the safety and efficacy of NTZ combined with cisplatin plus 5-fluorouracil (PF) as induction regimen in locally advanced nasopharyngeal carcinoma (NPC) patients receiving concurrent radiochemotherapy. METHODS:This was a multicenter randomized controlled study performed in eight Guangxi hospitals in 2015-2017. Eligible patients with NPC were randomized into nimotuzumab/PF (NPF group) and docetaxel/PF (DPF group) regimens, respectively, as induction therapy. After 2 cycles of induction therapy, all patients received cisplatin and concurrent intensity modulated radiation therapy (IMRT). Then, the two groups were compared for safety and efficacy. RESULTS:A total of 118 patients with stage III-IVa NPC were assessed, with 58 and 60 in the NPF and DPF groups, respectively. Compared with DPF treatment, NPF induction therapy showed a more pronounced effect on cervical lymph nodes (P = 0.036), with higher response rate (RR) (81% vs 60%). Compared with the DPF group, the NPF group showed significantly reduced leukopenia, neutropenia and gastrointestinal reactions (all P < 0.05); rash only appeared in the NPF group, but all cases were grade 1. During concurrent treatment with radiotherapy and chemotherapy, the NPF group showed better tolerance to radiotherapy and chemotherapy; neutropenia, anemia, gastrointestinal reactions, oral mucositis and radiation dermatitis in the NPF group were significantly reduced (P < 0.05). The expression rate of EGFR was 94.9% (112/118). Compared with the DPF group, patients with EGFR expression in the NPF group showed better response (77.8% vs 63.0%, P = 0.033). CONCLUSION:For locally advanced NPC patients receiving follow-up cisplatin and IMRT, nimotuzumab/PF for induction therapy has better lymph node response rate and milder adverse reactions than the DPF regimen. In addition, the patients have better tolerance in subsequent concurrent radiotherapy and chemotherapy; however, long-term efficacy needs further follow-up evaluation. TRIAL REGISTRATION:The registration number of the clinical trial is ChiCTR-OIC-16008201 and retrospectively registered on March 31, 2016.
10.1186/s12885-019-6459-6
A prospective study on neoadjuvant chemoradiotherapy plus anti-EGFR monoclonal antibody followed by surgery for locally advanced cervical cancer.
Lu Heming,Wu Yuying,Liu Xu,Jiang Hailan,Pang Qiang,Peng Luxing,Cheng Jinjian,Deng Shan,Gu Junzhao,Zhao Renfeng,Hu Xiaoxia,Chen Changyi,Yu Jinming
OncoTargets and therapy
BACKGROUND:To investigate the efficacy and safety of neoadjuvant chemoradiotherapy plus anti-epidermal growth factor receptor monoclonal antibody followed by surgery for locally advanced cervical cancer (LACC). PATIENTS AND METHODS:Patients with histologically proven LACC were enrolled into this prospective study. All patients received intensity-modulated radiation therapy with conventional fractionation. Weekly cisplatin or nedaplatin was administered concurrently with intensity-modulated radiation therapy. Nimotuzumab, a humanized anti-epidermal growth factor receptor monoclonal antibody, was given at a dose of 200 mg per week for 6 cycles. Approximately 1 month after the completion of neoadjuvant treatment, the patients were assessed for clinical tumor response and operability based on MRI and gynecological examination. For those who were considered to be candidates for surgery, radical hysterectomy, and pelvic lymph node dissection were performed 5-6 weeks after the completion of neoadjuvant therapy. RESULTS:Twenty-eight patients were enrolled. Clinical complete response and partial response were found in 8 (28.5%) and 20 (71.5%) patients, respectively. Four patients were not eligible for surgery and 2 patients refused surgery although they were assessed as surgical candidates. They were not included in this analysis. Radical hysterectomy and pelvic lymph node dissection were performed for the remaining 22 patients. Among them, 8 (36.4%) had complete pathology response, 9 (40.9%) presented with persistent atypical cells or cervical intraepithelial neoplasia, and 5 (22.7%) presented with macroscopic and/or microscopic residual disease, according to the pathological evaluation. Median follow-up time was 22 months (range, 5-39 months). The 2-year locoregional control rate, progression-free survival rate, distant metastasis-free survival rate, and overall survival rate were 95.0%, 85.2%, 84.0%, and 90.0%, respectively. Acute toxicities were mild in general and easily manageable. Chronic toxicities were mainly limited to grade 1. No severe late toxicities were observed. CONCLUSION:Concurrent chemoradiotherapy plus nimotuzumab followed by surgery is highly effective and safe in LACC. Further studies are warranted to confirm the findings.
10.2147/OTT.S164071
Long-Term Results of Concurrent Chemoradiotherapy Combined with Anti-EGFR Monoclonal Antibody Prior to Surgery in Locally Advanced Cervical Cancer: A Single-Institute Prospective Study.
Qing Defeng,Wu Yuying,Liu Xu,Jiang Hailan,Zhu Chaohua,Liu Pei,Dang Junming,Li Xianglong,Chen Zhaohong,Long Xianfeng,Pang Qiang,Peng Luxing,Deng Shan,Gu Junzhao,Zhao Renfeng,Chen Changyi,Lu Heming
Cancer management and research
Purpose:We aimed to evaluate the long-term survival outcomes of concurrent chemoradiotherapy (CCRT) combined with nimotuzumab followed by surgery in patients with locally advanced cervical cancer (LACC). Patients and Methods:Patients received whole pelvic intensity-modulated radiation therapy (IMRT) and concomitantly with weekly cisplatin (40 mg/m) or nedaplatin (30 mg/m) and weekly nimotuzumab (200 mg). After assessment of the treatment response, patients then underwent radical surgery. Results:Between June 2013 and July 2016, 33 patients with FIGO IB2-IIIB cervical cancer were recruited. Clinical complete response and partial response were observed in 8 (24.3%) and 23 patients (69.7%), respectively. Twenty-seven patients (81.8%) were successfully treated with radical hysterectomy and pelvic lymphadenectomy: 9 (33.3%) showed pathological complete response; 10 (37.1%) showed partial response and 8 (29.6%) presented with persistent macroscopic/microscopic residual carcinoma. For the intention-to-treat population, the median follow-up time was 53.7 months. Locoregional recurrence and distant metastases were observed in three and seven patients, respectively. The 5-year overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival were 81.5%, 72.7%, 90.9%, and 78.3%, respectively. Both acute and late toxicities were manageable and mainly limited to grade 1 or 2. Conclusion:Concurrent chemoradiotherapy combined with nimotuzumab followed by surgery for patients with LACC is safe and results in excellent long-term treatment outcomes. Further randomized controlled studies are warranted to confirm the findings.
10.2147/CMAR.S282372
Nimotuzumab Combined With Irradiation Enhances the Inhibition to the HPV16 E6-Promoted Growth of Cervical Squamous Cell Carcinoma.
Xu Zhonghua,Shu Hang,Zhang Fan,Luo Weiwei,Li Yan,Chu Jinjin,Zhao Qihong,Lv Yin
Frontiers in oncology
Human papillomavirus (HPV) 16 E6 has been proved to increase the radiosensitivity and lead to the EGFR overexpression in cervical cancer cells. In this study, to investigate the inhibition of nimotuzumab-mediated EGFR blockade combined with radiotherapy, we established a C33A cervical squamous cell line overexpressed HPV16-E6 and a nude mouse model bearing these cell lines. The CCK-8 assay was used to detect the effects of various treatments on the proliferation of C33A cells. Flow cytometry was used to detect the rates of apoptosis and cell cycle arrest. Gene transcription and protein expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. Immunohistochemical staining was used to evaluate protein expression in tumor tissue. We revealed that E6-overexpressing C33A cells grew faster and were more sensitive to radiotherapy than control cells and o. The expression levels of EGFR, as well as those of downstream signaling molecules AKT and ERK 1/2, were significantly upregulated in C33A cells that overexpressed E6. We observed that nimotuzumab combined with radiotherapy could enhance the inhibition of C33A cell growth induced by E6, both and . We also observed enhanced effect after combination on G2/M cell cycle arrest and apoptosis in E6-overexpressing C33A cells. Furthermore, the combined therapy of nimotuzumab and radiation remarkably reduced the protein expression levels of EGFR, AKT, ERK 1/2 , and . In conclusion, HPV16 E6 expression is positively correlated with levels of EGFR, AKT, and ERK 1/2 protein expression. The combined treatment with nimotuzumab and radiotherapy to enhance radiosensitivity in E6-positive cervical squamous cell carcinoma was related to enhanced G2/M cell cycle arrest and caspase-related apoptosis.
10.3389/fonc.2020.01327
Safety and efficacy of nimotuzumab combined with chemoradiotherapy in Chinese patients with locally advanced cervical cancer.
OncoTargets and therapy
OBJECTIVE:To evaluate efficacy and safety of nimotuzumab combined with chemotherapy and radiotherapy in women with locally advanced cervical cancer. MATERIALS AND METHODS:Women with locally advanced cervical cancer (stage IIB, III, or IVA) who experienced relapse after first-line chemoradiotherapy and one or more lines of palliative chemotherapy were enrolled. All patients received nimotuzumab weekly at 200 mg/m as single agent for 4 weeks (induction phase), then concurrent with 6 cycles (21-day per cycle) of gemcitabine (800 mg/m) or cisplatin (50 mg/m) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Overall response rate (ORR) was assessed after 4 weeks of induction therapy and then every 3 months according to response evaluation criteria in solid tumors version 1.1 (primary end point). Secondary end points include progression-free survival (PFS), overall survival (OS), and drug toxicity. Descriptive statistics was used for ORR, and Kaplan-Meier curves were generated for OS and PFS. RESULTS:A total of 80 women with locally advanced cervical cancer were enrolled and evaluated for safety and efficacy. Our results demonstrated that none of the patients had a complete response (0%), 11 patients had a partial response (14%), and 10 patients had progressive disease (13%), giving a tumor response rate of 14%. A total of 59 patients had stable disease (74%), giving a disease control rate of 88% (70/80). Median PFS was 8.21 months (95% confidence interval [CI]: 5.09-12.45). Median OS was 11.96 months (95% CI: 8.11-23.95). The most common adverse events were mucositis, myelosuppression, and gastrointestinal disturbance. CONCLUSION:Our study results suggested that nimotuzumab in combination with chemotherapy and radiotherapy is well tolerated, and could be a better treatment alternative in patients with locally advanced cervical cancer.
10.2147/OTT.S133756
Clinical study of nimotuzumab combined with concurrent radiochemotherapy for treatment of locally advanced cervical cancer.
Cancer management and research
PURPOSE:Nimotuzumab is a humanized monoclonal antibody that targets the epidermal growth factor receptor (EGFR) to inhibit tumor growth. Nimotuzumab has demonstrated desirable therapeutic activity in various types of tumors. However, the benefit of nimotuzumab for the treatment of cervical cancer is not entirely clear. The present study aimed to investigate the effects of nimotuzumab in the presence of CCRT in the first-line treatment of locally advanced cervical cancer (LACC). METHODS:The therapeutic efficacy and side effects of nimotuzumab combined with concurrent radiochemotherapy (CCRT) were retrospectively assessed in inoperable patients with LACC (stage IIb-IIIb) who were treated using CCRT with or without nimotuzumab. RESULTS:The complete response rate of study group was significantly better than control group (78.3% vs 50%, =0.035). The difference in median progression-free survival (PFS) in the two groups was statistically significan (not reach vs 27 months, =0.037). Multivariate comparisons of prognostic factors in the two groups indicated that both the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage and combined nimotuzumab treatment affected PFS (<0.05). Although generally tolerable, grade 3-4 toxicities including leukopenia (=0.025) and hemoglobin (=0.026) reduction were more frequent in the control group than those in the study group. CONCLUSION:These data suggest that combining nimotuzumab with CCRT for the treatment of LACC resulted in extended PFS and higher complete remission rates, without an increased incidence of adverse events.
10.2147/CMAR.S191134
A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent, persistent or metastatic cervical cancer.
Cetina Lucely,Crombet Tania,Jiménez-Lima Roberto,Zapata Sergio,Ramos Mayra,Avila Sandra,Coronel Jaime,Charco Eduardo,Bojalil Rafael,Astudillo Horacio,Bazán Blanca,Dueñas-González Alfonso
Cancer biology & therapy
Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m(2) as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m(2)) or cisplatin (50 mg/m(2)) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5-96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were 163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer.
10.1080/15384047.2015.1026483