Phase I evaluation of a biochemically designed combination: PALA, thymidine, and 5-FU

Fifteen patients with advanced solid tumors participated in a phase I study of a biochemically designed combination chemotherapy program which employed PALA and thymidine (TdR) with 5-FU. PALA (250-2000 mg/m2) was given 24 hours before a 90-minute iv infusion of TdR (45 g). 5-FU (100-150 mg/m2) was given as a rapid iv injection 30 minutes after beginning the TdR infusion. This three-drug treatment was repeated once weekly for 3 weeks. Neurotoxicity, manifested as dizziness, lethargy, and confusion, was dose-limiting. Myelosuppression was noted at all dose levels, as was mild to moderate mucositis and diarrhea. Further clinical evaluation of this combination does not appear to be warranted.