Chemotherapy for colorectal cancer with a combination of PALA and 5-FU

Fifty-one previously untreated patients with advanced, measurable colorectal cancer were randomized to receive single doses of PALA and 5-FU either weekly (24 patients) or daily for 5 days every 4 weeks (27 patients). In both schedules the daily dose of PALA was administered iv over 1 hour, while the dose of 5-FU was administered iv over 30 minutes, starting 3 hours after completion of the PALA dose. Doses of both drugs were changed simultaneously, based on toxic effects. Partial responses were seen in four of 24 evaluable patients receiving the weekly regimen and in three of 26 patients receiving the 5-day regimen. Skin rash, mucositis, and diarrhea were the dose-limiting toxic effects in both treatment regimens. These toxic effects were more common and severe at higher doses and on the weekly schedule. Myelosuppression was mild and moderate, the doses and schedules used in this study did not significantly increase the activity of 5-FU. Further evaluation of these doses and schedules for activity against colorectal cancer is not warranted.