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Docetaxel in Combined Modality Therapy for Breast Cancer

Docetaxel in Combined Modality Therapy for Breast Cancer

Since the emergence of paclitaxel (Taxol) in 1983, clinical development of the taxoids has progressed at a rapid pace, with the introduction of docetaxel (Taxotere) into clinical trials in 1990, and international phase II studies in 1992. Although these two taxoids are related, increasing clinical experience indicates that paclitaxel and docetaxel should not be considered interchangeable.

In "Docetaxel in Breast Cancer and a Rationale for Combination Therapy," I discuss some of the combination chemotherapy studies that have been conducted or are ongoing. The challenge is not only to find effective combinations, strategies, and regimens, but also to determine the optimal role for docetaxel in relation to many other active agents currently in development.

Doxorubicin has long been recognized as one of the most effective single agents used in the treatment of metastatic breast cancer, and doxorubicin combinations are among the most active in advanced or metastatic disease. These observations were included in the rationale for a feasibility study using doxorubicin and docetaxel in combination. In "Docetaxel in Combination With Doxorubicin: A Phase I Dose-Finding Study," Dr. Véronique Diéras reports on a phase I clinical trial using docetaxel in combination with doxorubicin for the treatment of metastatic or advanced disease.

In "Docetaxel and Cyclophosphamide in Patients With Advanced Solid Tumors," Dr. Vicente Valero reports on the design and initial results of a phase I study to evaluate efficacy and safety of docetaxel/cyclophosphamide combination therapy for metastatic breast cancer.

Also reported are two trials of docetaxel used in combination with doxorubicin and cyclophosphamide (Cytoxan, Neosar). A feasibility study was performed for the docetaxel arm of a larger phase III trial, in which docetaxel combined with doxorubicin and cyclophosphamide is used alone or as induction before high-dose chemotherapy, supplemented by autologous peripheral blood stem-cell transplantation. Preliminary results of this study are reportedby Dr. Nabholtz and colleagues in "Docetaxel/Doxorubicin/Cyclophosphamide in the Treatment of Metastatic Breast Cancer."

In "Docetaxel Combined With Vinorelbine: Phase I Results and New Study Designs," Dr. Pierre Fumoleau and colleagues report on a phase I dose-findingand pharmacokinetic study of vinorelbine (Navelbine) and docetaxel as first-line chemotherapy for metastatic breast cancer.

Dr. Rowinsky and colleagues present preliminary results of a phase I clinical trial testing the feasibility of docetaxel in combination with fluorouracil (5-FU) in their report "Docetaxel in Combination With Fluorouracil: Study Design and Preliminary Results."

In the final report in this supplement, "Preoperative Doxorubicin Plus Cyclophosphamide Followed by Preoperative or Postoperative Docetaxel," Dr. Eleftherios Mamounas discusses a National Surgical Adjuvant Breast and Bowel Program protocol involving the use of docetaxel as adjuvant therapy for early breast cancer.

Current or future clinical trials will evaluate docetaxel/anthracycline combinations in first-line therapy. One study will investigate the effects of scheduling, dosing interval, high-dose chemotherapy, and combination therapy with cyclophosphamide. Clinical trials of docetaxel combined with vinorelbine and 5-FU, with and without granulocyte-colony stimulating factor (G-CSF, filgrastim [Neupogen]), are also planned.

 
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