EFFECT OF CISPLATIN IN ADVANCED COLORECTAL-CANCER RESISTANT TO 5-FLUOROURACIL PLUS (S)-LEUCOVORIN

Modulation of 5-fluorouracil (5-FU) is currently being investigated in advanced colorectal cancer, In an attempt to improve the results obta inable for the association of 5-FU and leucovorin, we decided to add c isplatin to 5-FU and (6S)-leucovorin (S-LV) after disease progression. The hypothesis was that a pharmacological enhancement of the efficacy of 5-FU would result in responses in 5-FU-unresponsive patients or in a second response in previously responding patients. A group of 28 5- FU+S-LV-pretreated patients, with advanced measurable colorectal cance r, were treated with 80 mg/m(2) cisplatin on day 1, 80 mg/m(2) S-LV an d 370 mg/m(2) 5-FU as an i. v. bolus for 5 consecutive days every 4 we eks. We obtained 3 partial responses (response rate: 11+/-11%), while 11 patients had stable disease (39+/-18%). Among the 3 responders, 1 p atient had earlier achieved a partial response, a second stable diseas e and 1 had disease progression after the previous 5-FU+S-LV treatment . The median survival time for all 28 patients was 11 months, Toxicity was minimal and consisted of mild and reversible gastrointestinal sym ptoms and myelosuppression. We believe that further studies must be ca rried out to establish the real impact of the synergism between cispla tin, 5-FU and S-LV in untreated patients.