Docetaxel: an update of its use in advanced breast cancer.
Docetaxel, a semisynthetic member of the taxoid class of antineoplastic agents, is effective in the treatment of patients with advanced (locally advanced or metastatic) breast cancer. Reported objective response rates for docetaxel 100 mg/m2 ranged from 54 to 69% and 53 to 82% as first-line monotherapy or combination therapy, respectively. Objective response rates of 23 to 65% and 30 to 81% have been reported for docetaxel as second-line monotherapy or combination therapy, respectively. In Japanese studies, second-line docetaxel 60 mg/m2 produced objective response rates of 42 to 55%. At the recommended dose of 100 mg/m2 given as a 1-hour intravenous (i.v.) infusion every 3 weeks, docetaxel had significantly greater efficacy than doxorubicin, mitomycin plus vinblastine and methotrexate plus fluorouracil, and similar efficacy to fluorouracil plus vinorelbine in pretreated patients with advanced breast cancer. In chemotherapy-naive patients, first-line combined therapy with docetaxel and doxorubicin had significantly greater efficacy than doxorubicin plus cyclophosphamide. Promising results have been achieved in phase I/II trials of a weekly regimen of docetaxel (generally 30 to 45 mg/m2). Preliminary data indicate a potential role for docetaxel in the neoadjuvant therapy of early breast cancer. The major dose-limiting adverse event associated with docetaxel is neutropenia. Although other adverse events are common, the tolerability profile of docetaxel is generally acceptable in the majority of patients, particularly in comparison with other antineoplastic regimens.


CONCLUSIONS
Although no single standard regimen has been identified as optimal for the treatment of advanced breast cancer, phase III trials have shown that docetaxel has improved efficacy over doxorubicin alone (considered one of the current gold standards), methotrexate/fluorouracil and mitomycin/vinblastine in second-line therapy. In combination with doxorubicin, docetaxel has demonstrated better efficacy than doxorubicin/cyclophosphamide in first-line therapy. These results provide a basis for therapy choice in advanced breast cancer. Clinical trials comparing docetaxel monotherapy versus paclitaxel monotherapy and versus docetaxel combination therapy are warranted. The role of docetaxel in the adjuvant and neoadjuvant treatment of early breast cancer is being evaluated.
Figgitt
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DP
Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz
Wiseman
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LR
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002986:Clinical Trials as Topic; D000077143:Docetaxel; D004334:Drug Administration Schedule; D017850:Economics, Pharmaceutical; D005260:Female; D006801:Humans; D008657:Metabolic Clearance Rate; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D043823:Taxoids; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel