Nimotuzumab combined with gemcitabine and cisplatin as second‐line chemotherapy for advanced non‐small‐cell lung cancer

Abstract

Objective: To evaluate the efficacy and safety of nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) and to investigate the association of the status of KRAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome. Methods: Twenty-eight patients with advanced NSCLC were enrolled in this single center, uncontrolled pilot clinical study. All the patients developed drug resistance or disease progression after first-line chemotherapy of either a docetaxel + cisplatin regimen or a vinorelbine + cisplatin regimen and then received nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy. Eight cases were stage IIIB and 20 were stage IV.An i.v.dosage regimen of 200 mg of nimotuzumab was given as a single dose, injected into the patient at days 1, 8 and 15; i.v. gemcitabine was injected at a dose of 1000 mg/m 2 at days 1 and 8 and cisplatin (25 mg/m 2 i.v.) at days 1, 2 and 3. Each patient received four or more therapeutic cycles. The efficacy and toxic reactions were evaluated, as well as time to progression and overall survival. Results: In total, 28 patients with advanced NSCLC received 101 therapeutic cycles. The mean cycle number was 3.6. Median time to progression was 4.9 (2.5-6.5) months; median overall survival and 1-year survival rate were 9.8 months and 48.5%, respectively. There was one case of complete response, six cases of partial response, 11 cases of stable disease and 10 cases of progressive disease. Response rate was 25%, and clinical benefit rate was 64.3%. Major toxic reactions were bone marrow suppression and gastrointestinal reaction. Only one patient developed grade I acneiform eruption. Conclusion: Nimotuzumab combined with gemcitabine and cisplatin as secondline chemotherapy for advanced NSCLC was active and well-tolerated in this setting. Patients with EGFR amplification and KRAS gene wild type had a better prognosis. Prospective, randomized, controlled, large-scale clinical studies are needed to confirm the results.Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality and the incidence increases year by year.1-4 The majority of patients are at middle or late stage at the time of presentation, that is stage IIIB (locally advanced stage) or stage IV (metastatic).5-8 Through years of numerous clinical studies, the administration of platinum-based combination chemotherapy regimens, which standard chemotherapy for advanced NSCLC, have been constantly

Nimotuzumab plus chemotherapy versus chemotherapy alone in advanced non-small-cell lung cancer: a multicenter, randomized, open-label Phase II study

“…The docetaxel and carboplatin combination when administered to patients with stage IIIB/IV NSCLC resulted in an overall survival of 9.2 months27 and 9.4 months28 in two separate studies. Nimotuzumab in combination with gemcitabine and cisplatin as second-line therapy offered a median overall survival of 9.8 months 23. In our study, like overall survival, there were no significant between-group differences in progression-free survival ( P =0.31); the median progression-free survival of 4.9 months achieved in the nimotuzumab group was comparable with that of 4.44 months observed in another study using cetuximab in combination with a taxane 26…”

“…A study evaluating the efficacy of nimotuzumab plus gemcitabine and cisplatin as second-line therapy in patients with advanced NSCLC reported a response rate of 25% 23. In the Phase III FLEX (First-Line ErbituX in lung cancer) trial, treatment with cetuximab combined with cisplatin and vinorelbine resulted in a 36% overall response rate (measured by World Health Organization criteria) compared with 29% achieved with chemotherapy alone 25.…”

“…Earlier clinical studies of nimotuzumab plus radiation in patients with stage IIB, IIIB, or IV NSCLC have demonstrated that this combination therapy was well tolerated and feasible for patients unsuitable for radical therapy 21,22. Nimotuzumab combined with gem-citabine and cisplatin was also safe and tolerable in patients with advanced NSCLC 23. Additional studies evaluating the safety and efficacy of nimotuzumab in combination with various chemotherapeutic agents are ongoing 18…”

Nimotuzumab, a humanized monoclonal antibody specific for the EGFR, in combination with temozolomide and radiation therapy for newly diagnosed glioblastoma multiforme: First results in Chinese patients

“…[11][12][13][14][15] When combined with RT, nimotuzumab (200 mg/week) showed few side effects 16 and improved the disease control rate in GBM patients, as compared with patients treated with RT alone. 17 A randomized, multicenter phase III trial in Europe showed that nimotuzumab (400 mg, weekly) on top of the current standard radiochemotherapy with TMZ followed by biweekly infusions of 400 mg nimotuzumab, was well tolerated in newly diagnosed GBM patients, substantially improving their quality of life and showing a clear trend toward efficacy in O6-methylguanine-DNA methyltransferase (MGMT) non-methylated GBM patients.…”

Mucin Production Correlates with Dual Expression of Epidermal Growth Factor Receptor and Its Ligand the Epidermal Growth Factor in Non-Small Cell Lung Cancer

“…The other one is a humanized monoclonal antibody that directly binds the extracellular domain of the EGFR (nimotuzumab) [42]. Interestingly, promising results in advanced NSCLC patients treated with CIMAVax-EGF [43,44] or nimotuzumab [45,46] has been obtained. In this way, the evaluation of mucin production in NSCLC patients after CIMAVax-EGF or nimotuzumab treatment seems to be of utmost importance.…”