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

Abstract

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 thirdline 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 were163 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.

Safety and efficacy of nimotuzumab combined with chemoradiotherapy in Chinese patients with locally advanced cervical cancer

“…A pilot study was conducted to evaluate efficacy and safety of nimotuzumab in combination with chemotherapy among Caucasian patients with advanced or progressive cervical cancer. 12 The results of this study showed that nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer. However, to date, there has been no study that evaluates the efficacy and safety of nimotuzumab in combination with chemoradiotherapy in Chinese patients with locally advanced cervical cancer.…”

“…Overexpression of epidermal growth factor receptor (EGFR) in cervical cancer is well documented (overexpression ranges from 6% to 90%); this makes EGFR as a potential target in cervical cancer. 12 Nimotuzumab is a humanized IgG1 monoclonal antibody which blocks the activation of EGFR without intrinsic stimulating activity. Nimotuzumab displayed a longer plasma half-life with better safety profile when compared with other anti-EGFR antibodies.…”

“… 13 , 14 Nimotuzumab is approved in some countries for the treatment of glioma and advanced head and neck cancer as a single agent or in combination with chemotherapy and radiotherapy. 12 Efficacy and safety of nimotuzumab as a single agent or in combination with chemotherapy and radiation have been evaluated in cervical cancer; however, no results have been published. A pilot study was conducted to evaluate efficacy and safety of nimotuzumab in combination with chemotherapy among Caucasian patients with advanced or progressive cervical cancer.…”

Immunoscintigraphy With 99mTc-Nimotuzumab for Planning Immunotherapy in Patients With Bone Metastases Due to Prostate Cancer

“…This antibody has been extensively evaluated in patients with advanced cervical, head and neck, glioma, glioblastoma, lung, esophageal, pancreatic, and gastric cancers. [2][3][4][5][6][7] The main objectives of the studies performed to date have been to determine the toxicity, therapeutic effect, and biodistribution of the monoclonal antibody alone or as a delivery system for radioisotopes. Other studies have determined the in vivo specificity and the ratio of antibody uptake in tumor compared to normal tissues.…”

The safety and efficacy of bevacizumab in the treatment of patients with recurrent or metastatic cervical cancer

“…Nimotuzumab was well tolerated. There were no complete or partial responses observed; stable disease was found in 35% [34]. Study findings are limited as acceptability was addressed; however, study design excluded PFS and OS as endpoints.…”