Docetaxel, estramustine and prednisone for hormone-refractory prostate cancer: a single-center experience.
BACKGROUND
The results of chemotherapy in patients with advanced, hormone-refractory prostate cancer (HRPC) have been disappointing. Mitoxantrone has been used in the past for palliation, but it does not prolong survival. It was recently demonstrated that docetaxel is able to improve median survival as compared to mitoxantrone. We, therefore, wanted to evaluate a docetaxel-based regimen, with regard to efficacy and tolerability, in men with HRPC at our institution.


METHODS
Patients with progressive HRPC (new metastatic lesions or PSA progression) and no prior cytotoxic chemotherapy received the following treatment administered in 21-day cycles: 280 mg estramustine three times daily on days 1 to 5 and 7 to 11, 70 mg docetaxel per square meter of body surface area on day 2, and 10 mg prednisone once daily throughout the course. After four cycles, the patients were re-evaluated via PSA, blood counts, CT and bone scans. If no progression had occurred, two more cycles were given. Objective response rates, post-treatment declines in serum PSA levels, as well as side-effects, were recorded.


RESULTS
Thirty-nine patients with HRPC (age range 43-79 years, average 65 years) were enrolled after informed consent. The median PSA in this cohort was 144 (1.5-3030) ng/ml. The percentage of patients with bone and lymph node metastases was 82% and 61.5%, respectively. During an average follow-up period of 11 months, 20 patients (64.5%) showed a response to therapy, including a complete (CR), partial (PR) or mixed (MR) response, stable disease (SD) of metastatic lesions, or a PSA response. A post-therapeutic decrease of serum PSA levels of >25%, >50% and >75% occurred in 26.1%, 21.7% and 26.1% of patients, respectively. Lymph node metastases responded better to therapy (73%) than bone metastases (42%). Regarding toxicity, the regimen was generally well tolerated. Only three patients showed adverse events (one grade 4 neutropenia, one dermatological and one as a result of pain), which led to therapy withdrawal. Minor adverse events included nausea, alopecia and fatigue. No cardiovascular events were reported.


CONCLUSIONS
Although the patients included in the present study had advanced disease, responses were promising and toxicity was tolerable. These preliminary data support the findings of recently published studies and suggest that docetaxel-based chemotherapy is going to play an important role as a regimen for patients with HRPC.
Boehmer
Angela
A
Department of Urology, University of Tuebingen Medical Center, Tuebingen, Germany.
Anastasiadis
Aristotelis G
AG
Feyerabend
Susan
S
Nagele
Udo
U
Kuczyk
Markus
M
Schilling
David
D
Corvin
Stefan
S
Merseburger
Axel S
AS
Stenzl
Arnulf
A
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy; D011241:Prednisone / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage
D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D017430:Prostate-Specific Antigen; D011241:Prednisone