title: A phase I study of estramustine, weekly docetaxel, and carboplatin chemotherapy in patients with hormone-refractory prostate cancer.
abstract: 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.
authors.affiliation: Lank Center for Genitourinary Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Massachusetts 02115, USA. william_oh@dfci.harvard.edu
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hagmann
authors.forename: Judith
authors.initials: J
authors.lastname: Manola
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: George
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Gilligan
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Jacobson
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Smith
authors.forename: Donald S
authors.initials: DS
authors.lastname: Kaufman
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
mesh_terms: 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
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D016190:Carboplatin; D008942:Mitoxantrone; D007654:Ketoconazole