A phase I study of estramustine, weekly docetaxel, and carboplatin chemotherapy in patients with hormone-refractory prostate cancer.
OBJECTIVE
To define the maximal tolerated dose, safety, and efficacy of docetaxel, carboplatin, and estramustine in patients with hormone-refractory prostate cancer (HRPC).


METHODS
Patients with HRPC received docetaxel for 3 weeks, followed by a rest week. Docetaxel (20, 25, 30, 36, or 43 mg/m2) was given on days 2, 9, and 16 of a 28-day cycle. Patients also received estramustine (140 mg p.o. three times daily on days 1-5, 8-12, and 15-19) and carboplatin [area under the curve, AUC (5) or (6) on day 2].


RESULTS
Thirty patients were treated. Five patients received carboplatin [AUC (6)] but experienced delayed thrombocytopenia. After a protocol amendment, 25 subsequent patients received carboplatin [AUC (5)]. Median age was 64 years. Median prostate-specific antigen (PSA) was 117 ng/mL. Fifty-three percent received prior ketoconazole and 10% had mitoxantrone. No dose-limiting toxicities were noted. Although maximal tolerated dose was not reached, docetaxel dose escalation was stopped at 43 mg/m2. Significant myelosuppression was not seen until the highest dose level, when seven and four patients experienced grade 3 and 4 toxicities, respectively. Among all patients, PSA declines of > or =50% occurred in 63%. At the recommended phase II dose, PSA declines of > or =50% occurred in 75% (95% confidence interval, 43-95). Four of 14 (29%) patients with measurable disease had partial responses. Median survival was 14.6 months.


CONCLUSIONS
Estramustine, docetaxel, and carboplatin are well tolerated and active in HRPC. Myelosuppression is the primary toxicity. The recommended phase II dose of docetaxel is 43 mg/m2 combined with estramustine and carboplatin. PSA declines were seen at every dose level.
Oh
William K
WK
Lank Center for Genitourinary Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Massachusetts 02115, USA. william_oh@dfci.harvard.edu
Hagmann
Elizabeth
E
Manola
Judith
J
George
Daniel J
DJ
Gilligan
Timothy D
TD
Jacobson
Joseph O
JO
Smith
Matthew R
MR
Kaufman
Donald S
DS
Kantoff
Philip W
PW
D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004961:Estramustine / Q000008:administration & dosage*; D006801:Humans; D007654:Ketoconazole / Q000627:therapeutic use; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D043823:Taxoids / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D016190:Carboplatin; D008942:Mitoxantrone; D007654:Ketoconazole