A phase II study of estramustine, docetaxel, and exisulind in patients with hormone- refractory prostate cancer: results of cancer and leukemia group B trial 90004.
OBJECTIVE
Docetaxel/estramustine is a known active regimen in hormonerefractory prostate cancer (HRPC). A phase II study was conducted to assess the safety and efficacy of docetaxel/estramustine combined with exisulind, an apoptotic antineoplastic drug.


METHODS
Eighty men with chemotherapy-naive HRPC were enrolled in a multicenter, cooperative group study. The treatment regimen consisted of oral estramustine (280 mg 3 times daily for 5 days), docetaxel 70 mg/m2, oral exisulind (250 mg twice daily), oral dexamethasone (8 mg twice daily for 3 days), and oral warfarin (2 mg daily).


RESULTS
Seventy-five eligible patients were treated with a median of 6 cycles of therapy. Fortyseven patients (62.7%; 95% CI, 50.7%-73.6%) had a > or = 50% decline in prostate-specific antigen levels. Forty-six patients had measurable disease with 6 partial responses (13%; 95% CI, 4.9%-26.3%). The main grade 3/4 toxicities were neutrophils (79%), fatigue (15%), and thrombosis/embolism (10%). The median time to first progression was 5.1 months (95% CI, 4.4-6.3 months) and the median survival time was 17.8 months (95% CI, 14.7-20.1 months).


CONCLUSIONS
The combination of estramustine/docetaxel/exisulind was associated with significant thomboembolic toxicity despite prophylactic warfarin. The contribution of exisulind to toxicity is uncertain. Prostate-specific antigen decline, response rates, and progression-free and overall survival are similar to those reported with docetaxel/estramustine.
Dawson
Nancy A
NA
Georgetown University Medical Center, Washington, DC 20007-2113. USA. nad103@gunet.georgetown.edu
Halabi
Susan
S
Ou
San-San
SS
Biggs
David D
DD
Kessinger
Anne
A
Vogelzang
Nicholas
N
Clamon
Gerald H
GH
Nanus
David M
DM
Kelly
W Kevin
WK
Small
Eric J
EJ
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000077143:Docetaxel; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013467:Sulindac / Q000008:administration & dosage / Q000031:analogs & derivatives; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D013923:Thromboembolism / Q000139:chemically induced
D043823:Taxoids; D000077143:Docetaxel; D013467:Sulindac; D004961:Estramustine; D017430:Prostate-Specific Antigen; C025463:sulindac sulfone