Combining capecitabine, oxaliplatin, and gemcitabine (XELOXGEM) for colorectal carcinoma patients pretreated with irinotecan: a multicenter phase I/II trial.

PURPOSE

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.

METHODS

Patients with metastatic or recurrent CRC who failed after a first-line irinotecan-containing regimen received escalating doses of gemcitabine (600, 800, 1,000 mg/m(2) d1, d8) followed by capecitabine (1,000 mg/m(2) b.i.d d1-14) and oxaliplatin (100 mg/m(2) d1) on a 21-day cycle.

RESULTS

A total of 38 patients were treated. At 800 mg/m(2), two of six patients experienced dose-limiting toxicities (diarrhea and thrombocytopenia). Therefore, the clinically recommended dose was defined as 600 mg/m(2) gemcitabine (d1, d8) followed by 1,000 mg/m(2) capecitabine (b.i.d dl-14) and 100 mg/m(2) 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 response 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.