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

Abstract

BACKGROUND Current therapy for patients with carcinoma of an unknown primary site (CUP) is inadequate. To develop less toxic and more effective therapies for patients with CUP, a multicenter, randomized, Phase II study was conducted. 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/m2, intravenously over 3 hours on Day 1 followed by leucovorin, 300 mg, over 30–60 minutes and 5‐fluorouracil, 350 mg/m2, both intravenously on Days 1–3. Patients 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. The 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 interval, 4–45%) was noted in each treatment arm. The median survival for the entire study population was 194 days. The median survivals observed in Arm A and Arm B were 251 days and 194 days, respectively (P = 0.91 [difference not significant]). 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 reported with previously described chemotherapy regimens. Toxicity with CE was more severe than expected, although TFL was found to be well tolerated. Cancer 2001;91:592–7. © 2001 American Cancer Society.

Cancer of unknown primary site: review of consecutive cases at the National Cancer Center Hospital of Japan

“…3,6,7 Many combination regimens containing a taxane and/or platinum have been reported to yield objective response rates of approximately 20% to 40% and median survival times of 8 to 12 months in CUP subgroup without a specific therapy. [16][17][18][19][20][21][22][23][24][25] In our 35 patients who participated in the CDDP and docetaxel study, the response rate was 57.1% and the median survival time was 13.2 months. These results of chemotherapy for a CUP subgroup without a specific therapy suggest a modest improvement in efficacy compared with earlier chemotherapy studies.…”

Irinotecan plus carboplatin for patients with carcinoma of unknown primary site

“…The response rates to chemotherapy of patients with CUP have been reported as approximately in the range of 20 -40% (Briasoulis et al, 2000; Greco et al, 2000a, b;Dowell et al, 2001), so that the null hypothesis was that the true response rate was less than or equal to 30% (not considered to be clinically meaningful). The alternative hypothesis was that the true response rate was more than or equal to 50%.…”

A phase II study of mitomycin C, cisplatin and continuous infusion 5-fluorouracil (MCF) in the treatment of patients with carcinoma of unknown primary site

“…In the carboplatin-paclitaxel-etoposide study (Hainsworth et al, 1997), 24% of patients had node only disease and less than 40% had liver involvement. A randomised phase II comparison of paclitaxel, 5-FU and leucovorin vs carboplatin and etoposide (Dowell et al, 2001) in 34 patients, 62% of whom had liver metastases, yielded response rates of 19% in both arms, with median survival of less than 9 months, however, the small numbers in each arm again make interpretation difficult. More important than response rates and median survival data in CUP, where the majority of patients do not respond to chemotherapy, are longer term follow-up data.…”

“…Single agent chemotherapy studies in patients with ACUP show response rates for 5-fluorouracil (5-FU) and cisplatin of 0 -16% and 19% respectively (Johnson et al, 1964;Moertel et al, 1972;Schildt et al, 1983;Wagener et al, 1991). Numerous phase II studies have been performed with combination chemotherapy regimens (Anderson et al, 1983;Jadeja et al, 1983;van der Gaast et al, 1988;Becouarn et al, 1989;Treat et al, 1989;Hainsworth et al, 1997;Warner et al, 1998;Lofts et al, 1999;Briasoulis et al, 2000;Dowell et al, 2001;Greco et al, 2001;Guardiola et al, 2001), generally achieving response rates between 10 and 40%. More recently, the addition of paclitaxel, with its broad spectrum of activity, into combination regimens, has yielded response rates approaching 50% (Hainsworth et al, 1997;Greco et al, 2000).…”