Phase I clinical trial of taxotere administered as either a 2-hour or 6-hour intravenous infusion

• Published in: Journal of clinical oncology Vol. 11; no. 5; p. 950
• Main Authors: Burris, H, Irvin, R, Kuhn, J, Kalter, S, Smith, L, Shaffer, D, Fields, S, Weiss, G, Eckardt, J, Rodriguez, G
• Format: Journal Article
• Language: English
• Published: United States 01.05.1993
• Subjects: Adult; Aged; Antineoplastic Agents, Phytogenic - adverse effects; Antineoplastic Agents, Phytogenic - pharmacokinetics; Antineoplastic Agents, Phytogenic - therapeutic use; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Neoplasms - drug therapy; Neoplasms - metabolism; Paclitaxel - adverse effects; Paclitaxel - analogs & derivatives; Paclitaxel - pharmacokinetics; Paclitaxel - therapeutic use; Taxoids
• ISSN: 0732-183X
• DOI: 10.1200/JCO.1993.11.5.950

To determine the potential efficacy and dose-limiting toxicity of taxotere, a hemisynthetic inhibitor of tubulin depolymerization. Fifty-eight patients were administered taxotere in this phase I clinical trial as a 6-hour or a 2-hour infusion repeated every 21 days. Forty patients received 181 courses on the 6-hour infusion schedule, and 18 patients received 105 courses on the 2-hour infusion schedule. Neutropenia was the dose-limiting toxicity on both schedules. The maximally tolerated dose was 100 mg/m2 on the 6-hour infusion schedule and 115 mg/m2 on the 2-hour infusion schedule. The most prominent nonhematologic toxicities included mucositis (more prominent on the 6-hour infusion schedule), transient rash (more common on the 2-hour infusion schedule), and alopecia. Hypersensitivity reactions were seen in five patients. There was no evidence of neurotoxicity or cardiotoxicity. One partial response was noted on the 6-hour infusion schedule (one in refractory breast cancer) and four additional partial responses were noted on the 2-hour infusion schedule (two in adenocarcinoma of the lung, one in refractory breast cancer, one in cholangio-carcinoma). In addition, 10 patients had minor responses. Pharmacokinetic studies showed plasma concentrations of taxotere declined in a triexponential manner, with a terminal half-life of 11.8 hours. The recommended starting dose for phase II taxotere trials is 100 mg/m2 administered as a 2-hour infusion, repeated every 21 days. Taxotere is a promising antineoplastic agent worthy of extensive phase II testing in patients with a variety of malignancies.