Seminars in oncology
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Seminars in oncology · Jun 1999
ReviewDoxorubicin/taxane combinations: cardiac toxicity and pharmacokinetics.
Doxorubicin and the taxanes, paclitaxel and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA), are among the most active cytotoxic agents for the treatment of metastatic breast cancer. Given their activity, relative non-cross-resistance, partially non-overlapping toxicities, and differing mechanisms of action, there is a clear rationale for combining these agents for both advanced and early stage disease. Phase I and II trials have been reported for both doxorubicin/paclitaxel and doxorubicin/docetaxel. ⋯ This is likely explained by a pharmacokinetic interference of doxorubicin elimination by paclitaxel, an effect that is highly dependent on the interval between administration of the drugs and the duration of the paclitaxel drug infusion. Such an interaction has not been observed with doxorubicin/docetaxel, providing an explanation for the lack of enhanced cardiotoxicity with docetaxel-containing combination. Phase III trials comparing doxorubicin/taxane combinations with standard regimens have been completed and are in progress, and should help define whether the use of these drugs in combination offers any advantage over their use in a sequential fashion in both early and advanced disease.
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Seminars in oncology · Jun 1999
ReviewEmerging role of docetaxel (Taxotere) in the adjuvant therapy of breast cancer.
The need for improved adjuvant chemotherapy programs for breast cancer patients is emphasized by the 1998 overview analysis of adjuvant trials, which demonstrates that although there has been substantial incremental advances in adjuvant therapy, relapse and death are prevented in less than half of women with micrometastatic disease. Because both docetaxel (Taxotere; Rhône-Pouleuc Rorer, Collegeville, PA) and paclitaxel have substantial non-cross-resistance with anthracyclines and therefore activity in anthracycline-resistant breast cancer, defining their roles in the adjuvant therapy of breast cancer is an area of great interest and active clinical investigation. ⋯ Ongoing or soon-to-open adjuvant trials are evaluating the impact of docetaxel added to conventional adjuvant anthracyclines regimens, substituted for anthracyclines, used in combination with anthracyclines, and in direct comparison to paclitaxel. The results of these ongoing adjuvant trials will define the role of docetaxel in adjuvant chemotherapy programs for the management of patients with breast cancer and are eagerly awaited.
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Seminars in oncology · Jun 1999
Clinical TrialDocetaxel (Taxotere) administered in weekly schedules.
The administration of a weekly low-dose taxane markedly reduces the severity of myelosuppression compared with a once-every-3-week schedule and allows the dose intensity (mg/m2/wk) of treatment to be increased. The dose-limiting toxicity observed in a weekly phase I trial was fatigue/asthenia. The maximum tolerated dose of a weekly docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) phase I study was 43 mg/m2; 36 mg/m2 was recommended for further study. ⋯ Other studies have been conducted to evaluate the efficacy and safety of the weekly schedule. One such study is an ongoing phase II trial in elderly or medically unfit patients with previously untreated advanced non-small cell lung cancer in whom weekly docetaxel appears active and well tolerated. Further investigation of weekly docetaxel alone or in combination is warranted.