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
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.