A multicenter phase I/II trial of capecitabine, oxaliplatin and gemcitabine (XELOXGEM) in patients with advanced colorectal carcinoma pretreated with irinotecan

Abstract

Background: Capecitabine plus oxaliplatin (XELOX) is an effective second-line regimen for advanced colorectal carcinoma (CRC) patients pretreated with irinotecan. Previous studies have shown supra-additive anti-tumor activity of gemcitabine (GEM) when administered with oxaliplatin. We investigated the dose, toxicity, and efficacy of a second-line XELOXGEM regimen in CRC patients pretreated with irinotecan.Patients and methods: Patients with metastatic or recurrent CRC who failed after a first-line irinotecan-containing regimen received escalating doses of gemcitabine (600, 800, 1000 mg/m2 d1, d8) followed by capecitabine (1000 mg/m2 b.i.d d1-14) and oxaliplatin (100 mg/m2 d1) on a 21-day cycle.Results: A total of 38 patients were treated. At 800 mg/m2, two of six patients experienced dose-limiting toxicities (diarrhea and thrombocytopenia). Therefore, the clinically recommended dose was defined as 600 mg/m2 gemcitabine (d1, d8) followed by 1000 mg/m2 capecitabine (b.i.d d1-14) and 100 mg/m2 oxaliplatin (d1). The most common grade 3/4 toxicities were neutropenia (32%), thrombocytopenia (13%), anemia (11%) and peripheral neuropathy (11%). Ten (26.3%) and 23 (60.5%) patients experienced partial remission and stable disease, respectively. The median progression-free survival and overall survival were 5.4 months (95% CI 3.8-6.9 months) and 17.7 months (95% CI 8.4-26.9 months), respectively.Conclusions: The XELOXGEM triplet combination is an active and safe second-line regimen for advanced CRC patients pretreated with irinotecan.