A phase II trial of carboplatin, gemcitabine and capecitabine in patients with carcinoma of unknown primary site (CUP).

4090 Background: The prognosis for patients (pts) with CUP is poor, with a median survival of 4-6 mos. This trial was designed to evaluate the efficacy and toxicity of a novel chemotherapy combination (carboplatin, gemcitabine and capecitabine) in pts with CUP.,Treatment consisted of carboplatin AUC of 5 on day 1, gemcitabine 1000 mg/m by 30 minute intravenous infusion on days 1 and 8, and capecitabine 1,600 mg/m orally in divided doses days 1-14. Treatment was repeated every 21 days for a maximum of 8 cycles.,27 pts have been enrolled: median age 57 yrs (21-73); 17 men: 10 women; performance status 0/1/2: 9/10/8. Histology included 18 adenocarcinoma, 5 poorly differentiated adenocarcinoma and 4 undifferentiated carcinoma. 15 pts had hepatic involvement at presentation (56%). 22 pts are evaluable for response, 25 pts for toxicity (2 pts too early). Median number of cycles received was 4; median time-to-treatment failure was 4.6 mos (95% CI, 2.7-7.1). Partial response (PR) was seen in 9 pts (41%) and 7 pts (28%) had stable disease (SD) through at least 4 cycles. Median survival for all pts was 6.5 mos. (95% CI, 5.5-14.8), for those demonstrating PR/SD 14.8 mos (95% CI, 11.4-27.4). Myelosuppression was the major toxicity (grade 3:4 ANC 40%:24%, anemia 28%:0% platelets 36%:12%) with 4 episodes of neutropenic fever and one neutropenia-related death. 36% and 16% pts required 1 or 2 dose reductions of carboplatin and/or gemcitabine because of myelosuppression. One patient had a reduction of capecitabine due to stomatitis. Non-heme toxicity included grade 3 vomiting 8%, stomatitis 8%, hepatotoxicity 4%. Grade 4 non-heme toxicity was not seen.,The combination of carboplatin, gemcitabine and capecitabine is active and well tolerated in patients with CUP. Response rates and survival compare favorably with previously studied empiric regimens. Supported in part by Eli Lilly. [Table: see text].