Prospective randomized study comparing docetaxel, estramustine, and prednisone with docetaxel and prednisone in metastatic hormone-refractory prostate cancer.
OBJECTIVE
To assess the efficacy and toxicity of the addition of estramustine to docetaxel (D) for the treatment of metastatic hormone-refractory prostate cancer.


METHODS
One hundred fifty patients were randomly assigned to D alone (35 mg/m(2) on days 2 and 9, every 3 weeks) or D in combination with estramustine (D/E; 280 mg orally three times a day on days 1 to 5 and 8 to 12, every 3 weeks). All patients received prednisone (10 mg/d). The primary end point was prostate-specific antigen (PSA) response rate, which was defined as a decrease in PSA > or = 50% from baseline. The study was powered to test the hypothesis that D/E would improve the PSA response rate by 25%.


RESULTS
The PSA response rate was not statistically different between the two groups. PSA of less than 4 ng/mL occurred in 29 (41%) of 71 patients receiving D/E and in 17 (25%) of 69 patients receiving D (P = .05). No significant differences were found for median time to PSA progression (D/E, 6.9 months; D, 7.3 months) or median overall survival time (D/E, 19.3 months; D, 21 months). More patients had at least one grade 3 or 4 toxicity with D/E (45%) compared with D (21%; P = .005), mainly as a result of grade 3 or 4 GI toxicity (P = .05). Serious adverse events were more frequent with D/E (n = 20) than with D (n = 9; P = .04).


CONCLUSIONS
The addition of estramustine to weekly D does not provide any clinically relevant advantage. Both regimens are well tolerated, although the toxicity profile favors D without estramustine.
Machiels
Jean-Pascal
JP
Department of Medical Oncology and Urology, Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels, Belgium. Jean-pascal.Machiels@uclouvain.be
Mazzeo
Filomena
F
Clausse
Marylene
M
Filleul
Bertrand
B
Marcelis
Luc
L
Honhon
Brigitte
B
D'Hondt
Lionel
L
Dopchie
Catherine
C
Verschaeve
Vincent
V
Duck
Lionel
L
Verhoeven
Didier
D
Jousten
Peter
P
Bonny
Marie-Alix
MA
Moxhon
Anne-Marie
AM
Tombal
Bertrand
B
Kerger
Joseph
J
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001530:Belgium / Q000453:epidemiology; D018450:Disease Progression; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D017430:Prostate-Specific Antigen; D011241:Prednisone