A phase I study of docetaxel and 5-fluorouracil in patients with advanced solid malignancies

Purpose: This study was undertaken to evaluate the feasibility of administe ring docetaxel (Taxotere; Rhone-Poulenc-Rorer) as a one-hour intravenous (i .v.) infusion on day 1 combined with 5-fluorouracil (5-FU) as a bolus i.v. injection for five (days 1-5) or three (days 1-3) consecutive days every fo ur weeks. Patients and methods: Thirty-seven patients with advanced solid malignancie s were treated with 115 total courses involving seven dose levels of the tw o regimens of docetaxel and 5-FU (docetaxel/5-FU [mg/m(2)]/mg/m(2)/d]). In an effort to reduce fluid retention and hypersensitivity phenomena related to docetaxel, patients received premedication with dexamethasone 8 mg orall y twice daily for three consecutive days beginning 24 hours before treatmen t. Results: Severe (grade 4) neutropenia lasting longer than seven days with o r without fever and/or severe mucositis, precluded further dose escalation above docetaxel 60 mg/m(2) on day 1 and 5-FU 300 mg/m(2)/day administered o n days 1-5 every four weeks. The rates of these toxic effects were also una cceptably high above docetaxel 60 mg/m(2) on day 1 and 5-FU 300 mg/m2/day a dministered on days 1-3 every four weeks. Nine patients experienced various manifestations of fluid-retention that were potentially related to study d rugs. However, neither treatment delay nor discontinuation of treatment was required. Nausea, vomiting, diarrhea, and fatigue, were mild to modest in severity and occurred infrequently ( < 10% of courses). Two patients with m etastatic breast cancer experienced complete responses and a partial respon se occurred in a patient with metastatic non-small-cell lung cancer. Conclusion. Based on the results of this study, the regimen of docetaxel 60 mg/m(2) on day 1 followed by 5-FU 300 mg/m(2)/d i.v. for three or five day s every four weeks is well tolerated and these doses are recommended for fu rther evaluations. The feasibility of administering docetaxel 60 mg/m(2) fo llowed by 5-FU 300 mg/m(2) for three or five days every four weeks and the preliminary antitumor activity noted indicate that further disease-directed studies of docetaxel and 5-FU are warranted in patients with relevant soli d malignancies.