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Paclitaxel/Carboplatin/Etoposide Versus Gemcitabine/Irinotecan in the First-Line Treatment of Patients With Carcinoma of Unknown Primary Site: A Randomized, Phase III Sarah Cannon Oncology Research Consortium Trial

Hainsworth, John D. MD*†; Spigel, David R. MD*†; Clark, Bobby L. PhD*; Shipley, Dianna MD; Thompson, Dana S. MD; Farley, Cynthia CCRP*; West-Osterfield, Kimberly PhD*; Lane, Cassie M. MS*; Cescon, Terrence MD; Bury, Martin J. MD§; Greco, F. Anthony MD

doi: 10.1097/PPO.0b013e3181c6aa89
Original Article

Purpose: To compare the results of empiric first-line therapy with paclitaxel/carboplatin/etoposide (PCE) versus gemcitabine/irinotecan, both followed by single-agent gefitinib, in patients with carcinoma of unknown primary site.

Patients and Methods: Patients with previously untreated carcinoma of unknown primary site were randomized to receive either PCE or gemcitabine/irinotecan. Responding and stable patients continued treatment for 4 to 6 cycles. Patients with no evidence of tumor progression at that time received single-agent gefitinib until tumor progression. The trial was designed to detect an improvement in the 2-year survival rate from 20% to 30%.

Results: Between September 2003 and July 2008, 198 patients entered this multicenter, community-based trial. Because of slow accrual, the trial was stopped short of its target accrual of 320 patients. Clinical characteristics were comparable for patients receiving PCE (N = 93) and gemcitabine/irinotecan (N = 105). PCE and gemcitabine/irinotecan produced similar 2-year survival (15% vs. 18%), median survival (7.4 months vs. 8.5 months), median progression-free survival (3.3 months vs. 5.3 months), and response rate (18% vs. 18%). Grade 3/4 neutropenia, thrombocytopenia, anemia, febrile neutropenia, and red blood cells transfusions were more common with PCE; diarrhea was more common with gemcitabine/irinotecan. The median duration of gefitinib maintenance was 3 months, suggesting no role as a maintenance therapy in this setting.

Discussion: The PCE and gemcitabine/irinotecan regimens have comparable efficacy in the first-line treatment of patients with carcinoma of unknown primary site. Gemcitabine/irinotecan is the preferable regimen, due to its favorable toxicity profile. However, the moderate efficacy of both regimens underscores the need for novel treatment approaches in this patient population.

From the *Sarah Cannon Research Institute, Nashville, TN; †Tennessee Oncology PLCC, Nashville, TN; ‡Berks Hematology/Oncology Associates, Reading, PA; and §Grand Rapids CCOP, Grand Rapids, MI.

Reprints: John Hainsworth, MD, 3322 West End Ave, Suite 900, Nashville, TN 37203. E-mail:;

© 2010 Lippincott Williams & Wilkins, Inc.