Cisplatin i n C ombination W ith E ither G emcitabine o r Irinotecan i n C arcinomas o f U nknown P rimary S ite: R esults o f a R andomized P hase I I S tudy—Trial f or t he F rench S tudy Group o n C arcinomas o f U nknown P rimary ( GEFCAPI 0 1)

Purpose: To evaluate the efficacy and toxicity of novel chemotherapy combinations including cisplatin with gemcitabine (GC) or irinotecan (IC) for patients with carcinomas of an unknown primary site. Patients and Methods: Eighty patients were randomly assigned to receive GC or IC. In the GC arm, chemotherapy consisted of cycles combining gemcitabine 1,250 mg/m 2 intravenously (IV) on days 1 and 8, and cisplatin 100 mg/m 2 IV on day 1 at 3-week intervals. Patients in the IC arm originally received 3-week cycles of irinotecan 200 mg/m 2 IV on day 1 and cisplatin 80 mg/m 2 IV on day 1. After the inclusion of 15 patients in that arm, the toxicity profile required the irinotecan doses to be reduced to 150 mg/m 2 per cycle. Independent histologic and radiologic reviews were done. Results: A total of 78 patients were assessable for efficacy and toxicity. The median number of cycles was four in each arm. Objective responses were observed in 21 patients (55%) in the GC arm (95% CI, 34% to 66%) and in 15 patients (38%) in the IC arm (95% CI, 23% to 54%). Treatment had to be stopped because of toxicity in seven patients in the GC arm and in eight patients in the IC arm. With a median follow-up of 22 months, the median survivals were 8 and 6 months in the GC and IC arms, respectively. Conclusion: This study demonstrates the activity of both the GC and IC regimens. There was toxicity associated with both regimens. Additional studies of combination chemotherapy regimens are required. J Clin Oncol 21:3479-3482. © 2003 by American Society of Clinical Oncology.