SINGLE-AGENT INFUSIONAL 5-FLUOROURACIL IS NOT EFFECTIVE 2ND-LINE THERAPY AFTER RALTITREXED (TOMUDEX(R)) IN ADVANCED COLORECTAL-CANCER

Raltitrexed (Tomudex(R)) is currently licensed for first-line treatmen t of advanced colorectal cancer. We evaluated 101 patients treated wit h raltitrexed whose data were collected prospectively, in order to stu dy the outcome of second-line treatments used after this drug. Of 98 e valuable patients, 50 received second-line treatments, the commonest b eing 5-fluorouracil (5-FU)-based therapy (22 patients with 20 evaluabl e) and mitomycin-e (MMC) (22 patients with 18 evaluable). Only 1 respo nse was seen in a patient treated with 5-FU and MMC and none following other treatments. This patient was not evaluable for outcome of ralti trexed treatment, having stopped after two courses. Patients who had r esponded to raltitrexed and later progressed off treatment were more l ikely to be offered second-line 5-FU, but despite the earlier sensitiv ity to thymidylate synthase inhibition, response rates were minimal. U nderlying mechanisms for this lack of activity and proposals for futur e studies are discussed. (C) 1998 Elsevier Science Ltd. All rights res erved.