A phase I study of docetaxel, cisplatin, 5-fluorouracil and leucovorin

Objectives: Cisplatin, 5-fluorouracil (5-FU) and docetaxel are active agents in the treatment of upper gastrointestinal malignancies. This phase I study was undertaken to determine the maximally tolerated dose and dose-limiting toxicities of a combination of these drugs given in an ambulatory setting using a bolus schedule of 5-FU. Methods: Twenty patients with gastrointestinal malignancies were treated with docetaxel on day 1, cisplatin on day 2 and bolus 5-FU with leucovorin each day for 5 days, without prophylactic antibiotics or colony-stimulating factors. The cycle was repeated at 21-day intervals. A dose-escalating phase I design was used. Results: There were two treatment-related deaths as a result of neutropenia and sepsis. The maximally tolerated dose was docetaxel at 60 mg/m² on day 1, cisplatin at 75 mg/m² on day 2 and 5-FU at 200 mg/m² with leucovorin at 20 mg/m² daily from day 1 to day 5. At this dose, neutropenia was occurring in 4 of 6 patients treated. There were three partial responses, 1 patient with esophagogastric cancer and 2 with gastric cancer. Conclusions: This regimen demonstrates efficacy in upper gastrointestinal malignancies. Strategies to improve the tolerance of these agents in combination should be pursued.