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Docetaxel in prostate cancer
1Urologic Oncology Program, UCSF Comprehensive Cancer Center, 1600 Divisadero St., 3rd Floor, San Francisco, CA 94115, USA. smalle@medicine.ucsf.edu
Abstract:
In contrast to several other tumor types, there has been relatively little experience with docetaxel in hormone-refractory prostate cancer. However, two phase II trials investigated the combination of docetaxel with estramustine, and reported prostate-specific antigen response rates of 69 and 74% and objective responses in 23% and 57% of patients. This activity is comparable with that of other estramustine combinations. However, there is uncertainty about whether estramustine itself should be omitted from therapy because of its emetogenic and thromboembolic potential, and also over the optimal schedule of docetaxel to avoid neutropenia. Preliminary data suggest that weekly docetaxel, with or without limited exposure to estramustine, may provide the right balance between efficacy and tolerability. Phase III studies now in progress are comparing regimens containing docetaxel and estramustine with a recent standard therapy consisting of mitoxantrone plus prednisone. In the future, the efficacy of docetaxel plus estramustine may be enhanced by adding agents to this regimen.
Insights
Docetaxel combined with estramustine shows promise for hormone-refractory prostate cancer, with ongoing trials evaluating optimal dosing and potential combination therapies for improved efficacy and tolerability.
Area of Science:
- Oncology
- Urology
Background:
- Limited experience exists with docetaxel in hormone-refractory prostate cancer (HRPC).
- Estramustine combinations have shown activity but carry risks like nausea and blood clots.
- Optimal docetaxel scheduling is needed to mitigate neutropenia.
Purpose of the Study:
- To evaluate the efficacy and tolerability of docetaxel-based regimens in HRPC.
- To explore the potential benefits of combining docetaxel with estramustine.
- To identify optimal treatment schedules for docetaxel in HRPC.
Main Methods:
- Two Phase II trials investigated docetaxel combined with estramustine.
- Ongoing Phase III studies compare docetaxel/estramustine regimens with mitoxantrone/prednisone.
- Preliminary data analyzed weekly docetaxel schedules.
Main Results:
- Docetaxel-estramustine demonstrated high prostate-specific antigen response rates (69-74%) and objective responses (23-57%).
- Weekly docetaxel, with or without limited estramustine, suggests a balance of efficacy and tolerability.
- Ongoing Phase III trials are comparing these regimens to established standards of care.
Conclusions:
- Docetaxel-estramustine combinations show significant activity in HRPC.
- Weekly docetaxel regimens may offer an improved efficacy-tolerability profile.
- Future research will focus on optimizing docetaxel-based therapies and exploring novel combinations for HRPC.