Clinical experience with intravenous estramustine phosphate, paclitaxel, and carboplatin in patients with castrate, metastatic prostate adenocarcinoma.
BACKGROUND
The combination of paclitaxel, oral estramustine phosphate (EMP), and carboplatin (TEC) has shown antitumor activity in patients with castrate, metastatic prostate carcinoma. To improve the therapeutic efficacy and reduce the toxicity of TEC, the authors substituted intravenous (i.v.) EMP for oral EMP based on single-agent studies demonstrating an improved safety profile with i.v. EMP.


METHODS
Patients with progressive, castrate, metastatic prostate carcinoma were treated with up to 6 4-week cycles of i.v. EMP (500-1500 mg/m(2) per week), paclitaxel (100 mg/m(2) per week), and carboplatin (target area under the curve = 6 mg/mL every 4 weeks).


RESULTS
Thirty patients were treated in 6 dose cohorts. Deep venous thrombosis occurred in 5 of 30 patients (17%). Other common Grade 3/4 (according to National Cancer Institute Common Toxicity Criteria) toxicities included hepatic toxicity (23%) and leukopenia (24%). Posttherapy prostate specific antigen declines > 50% were seen in 18 of 30 patients (60%), and declines > 80% were seen in 15 of 30 patients (50%). Eleven of 17 patients (65%) with measurable soft tissue disease achieved a partial response. Four of 27 patients (15%) with osseous metastases demonstrated improvement on bone scan.


CONCLUSIONS
Intravenous EMP was administered safely with paclitaxel and carboplatin and produced clinical outcomes similar to the outcomes achieved with the TEC regimen. Substitution of i.v. EMP for the oral formulation was found to result in a lower incidence of severe nausea but increased hepatic toxicity.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
David B
DB
Solit
Michael
M
Morris
Susan
S
Slovin
Tracy
T
Curley
Lawrence
L
Schwartz
Steven
S
Larson
Michael W
MW
Kattan
Beryl
B
Hartley-Asp
Howard I
HI
Scher
W Kevin
WK
Kelly
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004961:Estramustine / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D004961:Estramustine; D016190:Carboplatin; D017430:Prostate-Specific Antigen; D017239:Paclitaxel