Randomized phase 2 study of irinotecan plus cisplatin versus gemcitabine plus vinorelbine as first‐line chemotherapy with second‐line crossover in patients with advanced nonsmall cell lung cancer

• Published in: Cancer 2008-07, Vol.113 (2), p.388-395
• Main Authors: Han, Ji‐Youn, Lee, Dae Ho, Song, Jung Eun, Lee, Sung Young, Kim, Hyae Young, Kim, Heung Tae, Lee, Jin Soo
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; cisplatin; Cisplatin - adverse effects; Cisplatin - therapeutic use; Cross-Over Studies; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Female; gemcitabine; Humans; irinotecan; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Neoplasm Staging; nonsmall cell lung cancer; Pneumology; Survival Rate; Tumors; Tumors of the respiratory system and mediastinum; Vinblastine - adverse effects; Vinblastine - analogs & derivatives; Vinblastine - therapeutic use; vinorelbine
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.23582

BACKGROUND. The current study was performed to compare the nonplatinum‐based combination of gemcitabine and vinorelbine (GV) with the combination of irinotecan and cisplatin (IP) as first‐line chemotherapy with second‐line crossover in patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. Patients were randomly assigned to received either irinotecan at a dose of 65 mg/m2 plus cisplatin at a dose of 30 mg/m2 (Arm A) or gemcitabine at a dose of 900 mg/m2 plus vinorelbine at a dose of 25 mg/m2 (Arm B), each of which was administered on Days 1 and 8 every 3 weeks as the first‐line therapy followed by crossover at the time of disease progression. RESULTS. A total of 146 patients were enrolled (75 patients in Arm A and 71 patients in Arm B); 138 patients were evaluable for tumor response and toxicity. During first‐line therapy, IP was found to result in more grade 2+ nausea and vomiting (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) (41% vs 12%; P = .0001) and alopecia (36% vs 10%; P = .0003). Pneumonitis was noted only with GV therapy (7% vs 0%; P = .058). During second‐line therapy, IP was found to result in more grade 3 diarrhea (17% vs 2%; P = .039) and GV featured more cases of grade 3+ neutropenia (78% vs 40%; P = .0003). IP tended to generate more tumor responses (38% vs 26% as first‐line therapy, and 30% vs 13% as second‐line therapy) compared with GV. IP also demonstrated a favorable trend in median progression‐free survival (4.6 months vs 3.8 months as first‐line therapy and 4.5 months vs 2.6 months as second‐line therapy) and overall survival (15.9 months vs 13.1 months; P = .3), but this difference was not statistically significant. The majority of patients who were refractory to IP also failed to respond to GV in the second‐line setting. CONCLUSIONS. The platinum‐based IP regimen appeared to be superior to the GV combination in terms of response rate. However, given the similar survival and better tolerability of the nonplatinum GV regimen, either treatment sequence would appear to be acceptable for the treatment of patients with advanced NSCLC. Cancer 2008. © 2008 American Cancer Society. Based on the favorable activity and tolerability of the combination of gemcitabine and vinorelbine reported in patients with nonsmall cell lung cancer (NSCLC), the authors conducted a phase 2 randomized trial to compare the nonplatinum‐based regimen of gemcitabine plus vinorelbine with that of t