Sequential methotrexate and 5-fluorouracil: improved response rate in metastatic colorectal cancer.

The efficacy of chemotherapy with sequential methotrexate (MTX) and 5-fluorouracil (5-FU) in metastatic colorectal cancer was studied in a multicenter phase II trial using a seven-hour time interval. Forty-two patients were evaluable for response and 16 achieved objective tumor regression (greater than 50%). Median survival of all patients was 12.5 months. The result of this study indicates that MTX and 5-FU are synergistic in human colorectal cancer if given sequentially with a seven-hour time interval. This is supported by a review of the literature that reveals a significantly higher response rate in patients treated with a four-hour or more MTX/5-FU interval as compared to a one-hour interval.