Phase II trial of 5-fluorouracil, high-dose leucovorin calcium, and dipyridamole in advanced prostate cancer

To examine the effect of altering intracellular folate pools on the efficacy of 5-fluorouracil (FUra) in the treatment of advanced prostate cancer, we performed a phase II trial of FUra (300-370 mg m^-2 day^-1×5 as an i.v. bolus) combined with high-dose folinic acid (500 mg m^-2 day^-1×5.5 days by continuous i.v. infusion) and dipyridamole (75 mg p.o. every 6h×5.5 days) administered on a 28-day schedule in patients with stage D₂ disease. A group of 13 patients have been treated. The median age was 68 years (range 48-78 years); the performance status ranged from 50% to 90%. Among 12 evaluable patients, there were no objective responders; the median time to progression was 1.9 months. Median survival after entry on this trial was 8.6 months. Treatment with FUra, high-dose folinic acid and dipyridamole was well tolerated. Only one episode each of grade 3 leukopenia, granulocytopenia, and thrombocytopenia was observed. These results suggest that, despite previous trials demonstrating activity for FUra in stage D₂ prostate cancer, this disease may be relatively resistant to fluoropyrimidines and, thus, less amenable to biochemical modulation with high-dose folinic acid and dipyridamole.