Taxoids in combination chemotherapy for metastatic breast cancer.
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Резюме
The rationale for the development of new drug combinations is to combine optimal doses of drugs with single agent activity which are not cross-resistant and have non-overlapping toxicities. Anthracyclines are widely accepted as the agents of choice for first-line treatment of metastatic breast cancer and have been tested in combination with the taxoids, docetaxel (Taxotere) and paclitaxel (Taxol). Toxicity problems have emerged using anthracyclines and paclitaxel, with sequence- and schedule-dependent toxic effects including dose-limiting typhlitis and mucositis, as well as febrile neutropenia and, in one study, cardiomyopathy. The dose-limiting toxicities of the combination of docetaxel and doxorubicin are neutropenia and infection, and preliminary results indicate a response rate of 89%. There is a need to develop a combination treatment regimen which is non-cross-resistant with anthracyclines. Vinorelbine (Navelbine) has single agent activity against metastatic breast cancer and has been used in combination with taxoids. The dose-limiting toxicities of the vinorelbine-paclitaxel combination are febrile neutropenia, pelvic pain, fatigue and paraesthesias. The dose-limiting toxicities of the combination of docetaxel and vinorelbine are febrile neutropenia and mucositis. The overall response rate for this combination was 67% and studies are ongoing.