Phase I study of 3-week schedule of irinotecan combined with cisplatin in patients with advanced solid tumors

Purpose: To assess the feasibility, pharmacokinetic interaction, and possib le sequence-dependent effects of the irinotecan/cisplatin combination given every 3 weeks, and to assess the influence of additional granulocyte colon y-stimulating factor (G-CSF) on the hematalogic toxicity. Patients and Methods: Patients who had received no more than one prior comb ination chemotherapy regimen or two single-agent regimens were entered, Tre atment consisted of a 90-minute irinotecan infusion followed by a 3-hour ci splatin infusion on day 1, with cycles repeated once every 3 weeks. After t he maximum-tolerated dose was determined, the sequence of administration wa r; reversed. In a separate cohort of six patients, we assessed the effect o f G-CSF on the experienced hematologic toxicity and dose-intensity. Irinote can doses ranged from 175 to 300 mg/m(2) and cisplatin doses ranged from 60 to 80 mg/m(2). Results: Fifty-two patients entered the study; one was not eligible, and tw o were not assessable for response. Twenty-five patients were pretreated, a nd 26 were not. Fifty-one patients received a total of 223 courses. The dos e-limiting toxicity was a combination of neutropenic fever, diarrhea, and f atigue at a dose level combining irinotecan 300 mg/m(2) with cisplatin 80 m g/m(2), Neutropenia was common (grades 3 to 4, 68%). Irinotecan pharmacokin etics were linear over the dose range studied. No sequence-dependent side e ffects were observed. Tumor responses included three complete responses and eight partial responses. Conclusion: For phase II studies, we recommend irinotecan 260 mg/m(2) combi ned with cisplatin 80 mg/m(2) once every 3 weeks for chemotherapy-naive pat ients in good physical condition, and irinotecan 200 mg/m(2) combined with cisplatin 80 mg/m(2) for other patients. (C) 2000 by American Society of Cl inical Oncology.