A randomized phase II trial in patients with carcinoma of an unknown primary site

BACKGROUND. Current therapy for patients with carcinoma of an unknown prima ry site (CUP) is inadequate. To develop less toxic and more effective thera pies for patients with CUP, a multicenter, randomized, Phase II study was c onducted. Patients with CUP received either carboplatin and etoposide (CE) or a combination of paclitaxel, 5-fluorouracil, and leucovorin (TFL). METHODS. Patients randomized to Arm A received paclitaxel, 175 mg/m(2), int ravenously over 3 hours on Day 1 followed by leucovorin, 300 mg, over 30-60 minutes and 5-fluorouracil, 350 mg/m(2), both intravenously on Days 1-3. P atients randomized to Arm B received etoposide, 100 mg/m2, intravenously on Days 1-3 and carboplatin at an area under the curve of 6 on Day 1 only. Th e cycles in both treatment arms were repeated every 28 days. Patients were followed for tumor response, survival, and toxicity. RESULTS. Thirty-four patients were enrolled, 32 of whom were evaluable for response. An identical overall response rate of 19% (95% confidence interva l, 4-45%) was noted in each treatment arm. The median survival for the enti re study population was 194 days. The median survivals observed in Arm A an d Arm were 251 days and 194 days, respectively (P = 0.91 [difference not si gnificant]). Hematologic toxicity on Arm B was considerable with 29% of the patients developing neutropenia and fever. Toxicity on Arm A was modest. CONCLUSIONS, In this randomized Phase II trial, CE and TFL appeared to have modest activity in CUP patients, with response rates similar to those repo rted with previously described chemotherapy regimens. Toxicity with CE was more severe than expected, although TFL was found to be well tolerated. (C) 2001 American Cancer Society.