Docetaxel

Jorge E. Cortes, Richard Pazdur

Research output: Contribution to journalReview article

422 Scopus citations

Abstract

Purpose: We reviewed the preclinical and clinical profiles at the antineoplastic taxoid docetaxel (Toxotere, Rhone-Poulenc Rorer, Collegeville, PA). Design: From the literature and manufacturer's data, we detail docetaxel's activity, tolerability, and pharmacokinetics in preclinical and phase I studies and its activity and side effects in phase II trials in various neoplasms. Results: Docetaxel promotes the assembly of and stabilizes microtubules, preventing their depolymerization. In phase I studies in patients with solid tumors refractory to standard chemotherapy, docetaxel's major dose-limiting toxicity (DLT) was dose- but not schedule-dependent neutropenia; another major side effect was schedule-dependent grade 3 mucositis. Other, generally less severe effects included hypersensitivity reactions (HSRs), neurotoxicities, cutaneous reactions, alopecia, and asthenia. Responses were observed in breast, bronchial, and ovarian carcinomas. The recommended dose for phase II studies was 100 mg/m2 as a 1- hour intravenous (IV) infusion every 3 weeks. Preliminary phase II results confirmed docetaxel's activity against breast, non-small-cell and small-cell lung, ovarian, head and neck, and gastric cancers; melanoma; and soft tissue sarcomas. Neutropenia again was the principal dose-limiting side effect. Nonhematologic effects, usually grade 1 or 2, including HSRs, were common. HSRs were manageable with premeditation. Corticosteroid premeditation partially alleviated fluid retention seen after repeated docetaxel courses. Studies are evaluating docetaxel in various combination regimens in advanced breast cancer, non-small-cell lung cancer, and other solid tumors. Conclusion: Multicenter and single-institution studies have demonstrated docetaxel's consistent significant activity in various cancers. Phase III and combination therapy trials are ongoing. Work is in progress to understand and prevent/resolve some of this drug's side effects.

Original languageEnglish (US)
Pages (from-to)2643-2655
Number of pages13
JournalJournal of Clinical Oncology
Volume13
Issue number10
DOIs
StatePublished - Oct 1995
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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