Efficacy of infusional biomodulated 5-fluorouracil in metastatic colorectal cancer after raltitrexed failure.

BACKGROUND Treatment of metastatic colorectal cancer (CRC) with raltitrexed results in an objective response rate (OR) and overall survival (OS) comparable to bolus 5-fluorouracil (5-FU). A phase III trial found raltitrexed to be inferior to continuous infusion of 5-FU (ci5-FU). PATIENTS AND METHODS This phase II trial studied the activity and toxicity of methotrexate-modulated ci5-FU (ci5-FU/MTX) after failure of raltitrexed in patients with metastatic CRC. RESULTS Of 32 patients who received raltitrexed, 27 were evaluable for response. An OR was observed in 19%. Grade 3/4 toxicity occurred in 47% of patients. Eighteen patients received second-line ci5-FU/MTX. One complete response (CR) and five stable diseases (SD) were observed. CR and SD were observed in patients with raltitrexed-resistant disease. Toxicity to ci5-FU/MTX was mild and predictable, even in patients with severe toxicity under raltitrexed. CONCLUSION ci5-FU/MTX is ineffective after failure of raltitrexed in patients with metastatic CRC. However, response to ci5-FU/MTX in patients with raltitrexed-resistant disease indicates incomplete cross-resistance.