A phase I study of irinotecan and infusional cisplatin for advanced non-small-cell lung cancer.

A phase I study was performed to establish the optimum dose for combination therapy with infusional cisplatin and irinotecan (CPT-11) in non-small-cell lung cancer (NSCLC). The subjects were 20 patients with a performance score of 0-2 with untreated advanced NSCLC. Cisplatin was administered by 5-day continuous intravenous infusion at 20-25 mg/m2 per day. CPT-11 was administered by bolus infusion at a starting dose of 20 mg/m2 on days 1 and 8 or 60 mg/m2 per day on day 1 alone, followed by serial increments of 20 mg/m2. Since grade 4 granulocytopenia was observed in two of the five patients receiving 20 mg/m2 per day cisplatin (days 1-5) and 100 mg/m2 CPT-11 (day 1), and since one of them developed severe pneumonia and sepsis associated with the granulocytopenia, the regimen was considered to be intolerable. In the same patient, grade 4 thrombocytopenia and grade 3 diarrhea were observed. Therefore, the optimum dose appeared to be 20 mg/m2 per day (days 1-5) for cisplatin and 80 mg/m2 (day 1) for CPT-11. The side effects were grade 2 diarrhea in one of three patients, and grade 2 vomiting in three patients, but grade > or = 2 hemotoxicity was not observed. This combined regimen resulted in a partial response in 9 out of 19 assessable patients. The dose-limiting factor in this combination therapy was granulocytopenia, and a high efficacy rate was obtained.