Purpose: The purpose of this study was to determine the maximum-tolerated dose and the dose-limiting toxicities of CPT-11, a new derivative of camptothecin, in combination with a fixed dose of cisplatin in patients with non-small-cell lung cancer (NSCLC).
Patients and methods: Twenty-seven previously untreated patients with stage IIIB or IV NSCLC were assessable for toxicity, and 26 were assessable for response. The initial dose of CPT-11 was 30 mg/m2 given as a 90-minute intravenous (IV) infusion on days 1, 8, and 15 in combination with cisplatin (80 mg/m2 IV on day 1) given every 4 weeks. The dose of CPT-11 was escalated in increments of 10 mg/m2 until severe or life-threatening toxic effects were observed.
Results: Significant toxicity was infrequent up to 60 mg/m2 of CPT-11. The maximum-tolerated toxicity was reached at a dose of 70 mg/m2. Three of six patients either had leukocyte count nadirs of less than 2,000/microL or experienced grade 4 diarrhea during the first cycle of therapy at 70 mg/m2. The major toxic effects were leukopenia and diarrhea. There were 14 partial responses (54%) among the 26 patients.
Conclusions: A combination of CPT-11 and cisplatin seems to be effective against NSCLC with acceptable toxicities. The recommended dose for phase II studies is 60 mg/m2 of CPT-11 on days 1, 8, and 15, and 80 mg/m2 of cisplatin on day 1 every 4 weeks.