Phase I Trial of Dipyridamole with 5-Fluorouracil and Folinic Acid

摘要: We have performed two Phase I trials of the combination dipyridamole, 5-fluorouracil (5-FU), and folinic acid in patients with advanced refractory malignancy, based upon vitro evidence that dipyridamole can modulate cytotoxicity 5-FU. In first trial, were treated every 4 wk (50 mg/m2) p.o. 6 h on Days 0 to 6, beginning 24 prior i.v. administration (200 escalating doses 5-FU 1 5. The maximum tolerated daily dose could be given this was 375 mg/m2. Because is extensively bound plasma proteins, it hypothesized concentrations free achieved a 50 mg/m2 inadequate acid. Therefore, second trial performed. Folinic (375 5 wk, after start therapy dipyridamole; administered at 75, 100, 125, 150, 175, or 200 mg/m2/dose successive cohorts patients. Dose-limiting neutropenia, mucositis, nausea produced mg/m2/dose; recommended for use II studies 175 h, 700 mg/m2/day. At dose, mean peak concentration total 16.32 mumol 38.30 nmol observed. Trough averaged 60% concentrations. Objective antitumor responses seen number tumor types; five 13 breast cancer high-dose 5-FU, responded. High-dose produce within range shown other agents. are justified.