title: Docetaxel, estramustine, plus trastuzumab in patients with metastatic androgen-independent prostate cancer.
abstract: The incidence of human epidermal growth factor receptor 2 (HER2) protein overexpression and its prognostic value are not well characterized in patients with prostate cancer. A phase I study was designed to evaluate docetaxel/estramustine plus trastuzumab, a humanized monoclonal antibody that binds to the HER2 receptor, in patients with metastatic androgen-independent prostate cancer (AIPC). HER2 positivity was not required because safety was the primary endpoint. Patients received oral estramustine 280 mg three times daily (days 1 to 5); docetaxel, 70 mg/m(2) intravenously (day 2); and trastuzumab, 2 mg/kg intravenously (days 2, 9, and 19), every 21 days until the disease progressed or toxicity became unacceptable. This regimen was well tolerated among the first 13 treated patients. Grade 4 neutropenia was seen in 10% of administered cycles. There were two episodes of febrile neutropenia and two thrombembolic events. Of the 13 patients evaluable for prostate-specific antigen (PSA) response, nine (69%) experienced a decrease in PSA level of >50%. Two (33%) of six patients with measurable disease had objective responses, and one complete response was seen on bone scan. Docetaxel/estramustine/trastuzumab appears to be a safe combination when used in the treatment of metastatic AIPC. The response data are too preliminary for speculation about the relative benefits of this 3-drug regimen compared with the combination of only docetaxel and estramustine in this clinical setting.
authors.affiliation: Urologic Oncology Program, University of California, San Francisco Comprehensive Cancer Center, San Francisco, CA 94143-1711, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Small
authors.forename: R
authors.initials: R
authors.lastname: Bok
authors.forename: D M
authors.initials: DM
authors.lastname: Reese
authors.forename: D
authors.initials: D
authors.lastname: Sudilovsky
authors.forename: M
authors.initials: M
authors.lastname: Frohlich
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D004961:Estramustine / Q000008:administration & dosage; D018734:Genes, erbB-2; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D000068878:Trastuzumab; D017239:Paclitaxel