Clinical studies of irinotecan alone and in combination with cisplatin.
Irinotecan (CPT-11), a new derivative of camptothecin, showed schedule-dependent antitumor activity and toxicity in preclinical animal studies. We carried out a phase I study of weekly CPT-11 infusion, which indicated that the recommended dose for phase II studies was 100 mg/m2. In a phase II trial, CPT-11 achieved a response rate of 32% for non-small cell lung cancer (NSCLC). In two phase II trials, CPT-11 achieved objective response rates of 37% and 47% for small cell lung cancer (SCLC). The high activity of CPT-11 in these phase II studies suggested that the next rational step was to investigate combination chemotherapy. The first phase I trial of CPT-11 combined with cisplatin achieved an encouraging response rate of 54% in 27 patients with previously untreated NSCLC, and the recommended schedule for phase II studies was 60 mg/m2 of CPT-11 (days 1, 8, and 15) plus 80 mg/m2 of cisplatin (day 1) given at 4-week intervals. Given the high single-agent activity of CPT-11 against SCLC and NSCLC, a regimen with a higher dose of this agent and a lower dose of cisplatin seemed likely to be more effective. In the second trial, the cisplatin dose was accordingly reduced from 80 to 60 mg/m2, and the recommended dose of CPT-11 was concluded to be 80 mg/m2. Thus, reduction of the cisplatin dose to 60 mg/m2 allowed the safe administration of CPT-11 at 80 mg/m2 (33.3% dose intensification compared with the original regimen). The most recent trial of this combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) support demonstrated that the recommended dose is 80 mg/m2 of CPT-11 and 80 mg/m2 of cisplatin. Thus, we could raise the CPT-11 dose 33% above that given in the original regimen while maintaining the original cisplatin dose by the use of rhG-CSF support. Further trials are needed to evaluate the effect of CPT-11 given in combination with other active agents for the treatment of lung cancer.
Fukuoka
M
M
Department of Internal Medicine, Osaka Prefectural Habikino Hospital, Japan.
Masuda
N
N
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin