Phase-I trial of combination therapy with continuous-infusion MMPR and continuous-infusion 5-FU.

Fourty-four evaluable patients were treated with 6-methylmercaptopurine riboside (MMPR) at a dose of 20 mg/m2/day X 5 by continuous IV infusion (days 1-5 and 5-fluorouracil (5-FU) on an escalating dose schedule of 300-1519 mg/m2/day X 5 by continuous IV infusion (days 2-6). Dose-limiting oral mucositis occurred at a 5-FU dose of 1,381 mg/m2/day; other toxicities included nausea, vomiting, diarrhea, skin rash, and occasional myelosuppression. A partial and a complete response were observed in two previously untreated patients with metastatic colon carcinoma given the highest 5-FU doses (1,381 and 1,519 mg/m2/day). Bone marrow phosphoribosyl pyrophosphate (PRPP) levels monitored after 24 h of MMPR treatment indicated increases of 7.8- and 9.2-fold those found prior to therapy.