Clinical studies of irinotecan alone and in combination with cisplatin.

Abstract

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.

• Authors: M Fukuoka, N Masuda
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 34 Suppl Pg. S105-11 ( 1994) ISSN: 0344-5704 [Print] Germany
• PMID: 8070018 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Irinotecan
• Cisplatin
• Camptothecin

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (toxicity)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use, toxicity)
• Camptothecin (administration & dosage, analogs & derivatives, therapeutic use, toxicity)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Carcinoma, Small Cell (drug therapy, pathology)
• Cisplatin (administration & dosage)
• Drug Administration Schedule
• Female
• Humans
• Irinotecan
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Staging