Is there a palliative benefit of gemcitabine (G) plus fluoropyrimidines (F) in patients (pts) with refractory colorectal cancer (CRC)?

Abstract

20655 Background: CRC is the second most common cause of cancer-related mortality in Europe and North America. Integration of newer cytotoxic and targeted agents have significantly improved the survival of pts with CRC. Pts with CRC are living longer, and challenges arise to offer them palliative treatment after they fail standard regimens. F (5-FU/capecitabine) with oxaliplatin or irinotecan are the most commonly used regimens in pts with advanced CRC. G, a nucleoside analog of deoxycytidine acts synergistically with F to enhance binding of thymidylate synthase and increase inhibition of DNA synthesis. Studies have indicated that F + G (FG) can be combined with acceptable toxicity at nearly full doses. FG could be an alternative for refractory CRC pts who failed standard therapy and have limited options. The objective of this review is to evaluate literature for evidence of efficacy and safety of FG in treating refractory CRC pts. Methods: PubMed (1950 through 2007), Ovid, Cochran and the American Society of Clinical Oncology abstract database were searched using the terms gemcitabine, fluorouracil, capecitabine, and colorectal cancer to identify relevant studies. Only studies using FG in CRC pts were reviewed and analyzed. Results: Forty-two advanced CRC pts were evaluated in two phase I studies and 179 pts were evaluated in five phase II studies. FG was used as 1st line therapy in two studies and as 3rd line therapy in three studies. The overall response rate (ORR), stable disease (SD), median time to tumor progression (TTP), and median overall survival (OS) were reported in the Tablebelow. The most commonly reported grade 3–4 toxicities were neutropenia, thrombocytopenia, and mucositis. Conclusions: FG is clinically active in pts with refractory CRC with prolonged median TTP and acceptable toxicities. FG may be considered for pts with advanced CRC refractory to primary treatment without other options or not eligible for clinical studies. Studies are underway to evaluate FG with other agents. Efficacy and Safety of FG in Treatment of Advanced CRC Phase (N) Regimen (Dose) Response Rate Grade 3-4 toxicity I (42) Gemcitabine (900-1,000 mg/m2) with either 5-FU (450 mg/m2)/folinic acid (100 mg/m2) or capecitabine (1,660 mg/m2/day) ORR: 38% Anemia: 7% Neutropenia: 7-11% II (179) Gemcitabine (900-1,250 mg/m2) with either 5-FU (200 mg/m2 CI or phase I dose) or capecitabine (2,500 mg/m2/day) ORR: 30-38.3% Neutropenia: 4-31% SD: 45-70.5% Thrombocytopenia: 6-18% TTP: 4-8.3 + months Mucositis: 5-8% No significant financial relationships to disclose.