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 obtainable for the association of 5-FU and leucovorin, we decided to add cisplatin 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 cancer, were treated with 80 mg/m2 cisplatin on day 1, 80 mg/m2 S-LV and 370 mg/m2 5-FU as an i. v. bolus for 5 consecutive days every 4 weeks. We obtained 3 partial responses (response rate: 11 +/- 11%), while 11 patients had stable disease (39 +/- 18%). Among the 3 responders, 1 patient had earlier achieved a partial response, a second stable disease 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 symptoms and myelosuppression. We believe that further studies must be carried out to establish the real impact of the synergism between cisplatin, 5-FU and S-LV in untreated patients.