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 combin ation 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/m(2) per day. CPT-11 was administered by bolus infusion at a starting dose of 20 mg/m(2) on days 1 and 8 or 60 mg/m(2) per day on day 1 alone, f ollowed by serial increments of 20 mg/m(2). Since grade 4 granulocytop enia was observed in two of the five patients receiving 20 mg/m(2) per day cisplatin (days 1-5) and 100 mg/m(2) CPT-11 (day 1), and since on e of them developed severe pneumonia and sepsis associated with the gr anulocytopenia, the regimen was considered to be intolerable. In the s ame patient, grade 4 thrombocytopenia and grade 3 diarrhea were observ ed. Therefore, the optimum dose appeared to be 20 mg/m(2) per day (day s 1-5) for cisplatin and 80 mg/m(2) (day 1) for CPT-11. The side effec ts were grade 2 diarrhea in one of three patients, and grade 2 vomitin g in three patients, but grade greater than or equal to 2 hemotoxicity was not observed. This combined regimen resulted in a partial respons e in 9 out of 19 assessable patients. The dose-limiting factor in this combination therapy was granulocytopenia, and a high efficacy rate wa s obtained.