[Sequential methotrexate and 5-fluorouracil].

There are two purported biochemical mechanisms to explain the sequence-dependent synergy between methotrexate (MTX) and 5-fluorouracil (5-FU). One hypothesis is to increase incorporation of FU-TP into RNA and another is more sustained inhibition of DNA synthesis. Clinical studies on MTX.5-FU, significantly higher response rates and longer survival have been reported in gastric and colorectal cancer, especially high dose MTX.5-FU and adriamycin (FAMTX) in gastric cancer. An optimal schedule for treatment has not yet been found. Reviewing data from the literature, a one-3 hour interval between the two drugs in gastric cancer and 3-8 hours in colorectal cancer seems to obtain better results. Sequential MTX.5-FU seems to be a very promising combination.