Single agent infusional 5-fluorouracil is not effective second-line therapy after raltitrexed (Tomudex) in advanced...

Raltitrexed (Tomudex) is currently licensed for first-line treatment of advanced colorectal cancer. We evaluated 101 patients treated with raltitrexed whose data were collected prospectively, in order to study the outcome of second-line treatments used after this drug. Of 98 evaluable patients, 50 received second-line treatments, the commonest being 5-fluorouracil (5-FU)-based therapy (22 patients with 20 evaluable) and mitomycin-c (MMC) (22 patients with 18 evaluable). Only 1 response was seen in a patient treated with 5-FU and MMC and none following other treatments. This patient was not evaluable for outcome of raltitrexed treatment, having stopped after two courses. Patients who had responded to raltitrexed and later progressed off treatment were more likely to be offered second-line 5-FU, but despite the earlier sensitivity to thymidylate synthase inhibition, response rates were minimal. Underlying mechanisms for this lack of activity and proposals for future studies are discussed.