Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer

• Published in: British journal of cancer Vol. 88; no. 3; pp. 335 - 341
• Main Authors: NEGORO, S, MASUDA, N, TAKADA, Y, SUGIURA, T, KUDOH, S, KATAKAMI, N, ARIYOSHI, Y, OHASHI, Y, NIITANI, H, FUKUOKA, M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 10-02-2003
• Subjects: Adolescent; Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - adverse effects; Camptothecin - analogs & derivatives; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Chemotherapy; Cisplatin - administration & dosage; Cisplatin - adverse effects; Clinical; Female; Humans; Irinotecan; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Survival Rate; Treatment Outcome; Antineoplastic agent; Phase III trial; Intravenous administration; Bronchopulmonary; non-small-cell lung cancer randomised phase III trial; Alkaloid; Randomization; Isomerases; Bronchus disease; Advanced stage; Antimitotic; Non small cell carcinoma; Platinum II Complexes; Human; Lung disease; DNA topoisomerase (ATP-hydrolysing); Drug combination; Respiratory disease; Enzyme; Vindesine; Enzyme inhibitor; Malignant tumor; Cisplatin; Irinotecan; Alkylating agent; Chemotherapy; Treatment; Comparative study
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600725

To determine a standard combination chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC), we conducted a phase III trial of irinotecan (CPT-11) to test the hypotheses that CPT-11+cisplatin is superior to cisplatin+vindesine and that CPT-11 monotherapy is not inferior to cisplatin+vindesine. A total of 398 patients with previously untreated NSCLC were randomised to receive cisplatin+CPT-11 (CPT-P), cisplatin+vindesine (VDS-P) or CPT-11 alone (CPT). In the CPT-P arm, CPT-11 60 mg m(-2) was administered on days 1, 8 and 15, and cisplatin 80 mg m(-2) was administered on day 1. In the VDS-P arm, cisplatin 80 mg m(-2) was administered on day 1, and vindesine 3 mg m(-2) was administered on days 1, 8 and 15. In the CPT arm, CPT-11 100 mg m(-2) was administered on days 1, 8 and 15. The median survival time was 50.0 weeks for patients on CPT-P, 45.6 weeks for those on VDS-P and 46.0 weeks for those on CPT (P=0.115, CPT-P vs VDS-P; P=0.089, CPT vs VDS-P), and the hazard ratio was 0.85 (95% confidence interval (CI): 0.65-1.11) for CPT-P vs VDS-P and 0.83 (0.64-1.09) for CPT vs VDS-P. The response rate was 43.7% for patients on CPT-P, 31.7% for those on VDS-P and 20.5% for those on CPT. Major adverse reactions were grade 4 neutropenia observed in 37, 54 and 8% of the patients on CPT-P, VDS-P and CPT, respectively; and grades 3 and 4 diarrhoea observed in 12, 3 and 15% of the patients, respectively. CPT-P therapy produces comparable survival to VDS-P in patients with advanced NSCLC. CPT-11 monotherapy is not inferior to VDS-P in terms of survival. The CPT-11-containing regimen is one of the most efficacious and well tolerated in the treatment of advanced NSCLC.