Multicenter randomized phase II study of two schedules of docetaxel, estramustine, and prednisone versus mitoxantrone plus prednisone in patients with metastatic hormone-refractory prostate cancer.
OBJECTIVE
Mitoxantrone-corticosteroid is currently the standard palliative treatment in hormone-refractory prostate cancer (HRPC) patients. Recent clinical trials documented the high activity of the docetaxel-estramustine combination. We conducted a randomized phase II study to evaluate prostate-specific antigen (PSA) response (primary end point) and safety of two docetaxel-estramustine-prednisone (DEP) regimens and mitoxantrone-prednisone (MP).


METHODS
One hundred thirty metastatic HRPC patients were randomly assigned to receive docetaxel (70 mg/m2 on day 2 or 35 mg/m2 on days 2 and 9 of each 21-day cycle) and estramustine (280 mg p.o. tid on days 1 through 5 and 8 through 12) or mitoxantrone 12 mg/m2 every 3 weeks; all patients received prednisone (10 mg daily).


RESULTS
One hundred twenty-seven patients were assessable for PSA response and safety. A > or = 50% PSA decline was found in a greater percentage of patients in the docetaxel arms (67% and 63%) compared with MP (18%; P = .0001). Median time to PSA progression was five times longer with DEP than with MP (8.8 and 9.3 v 1.7 months, respectively; P = .000001). Overall survival was better in the docetaxel arms (18.6 and 18.4 months) compared with the MP arm (13.4 months), but not significantly so (P = .3). Crossover rates differed significantly among treatment arms (16%, 10%, and 48% in arms A, B, and C, respectively; P = .00001). Treatment-related toxicities were mild and mainly hematologic.


CONCLUSIONS
The results of this randomized phase II study showed significantly higher PSA decline < or = 50% and longer times to progression in HRPC patients receiving DEP-based chemotherapy than MP, and that DEP could be proposed in this setting.
Oudard
Stéphane
S
Department of Medical Oncology, Georges Pompidou European Hospital, 20 Rue Leblanc, 75908, Paris Cedex 15, France. stephane.oudard@hop.egp.ap-hop-paris.fr
Banu
Eugeniu
E
Beuzeboc
Philippe
P
Voog
Eric
E
Dourthe
Louis Marie
LM
Hardy-Bessard
Anne Claire
AC
Linassier
Claude
C
Scotté
Florian
F
Banu
Adela
A
Coscas
Yvan
Y
Guinet
François
F
Poupon
Marie-France
MF
Andrieu
Jean-Marie
JM
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004961:Estramustine / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D043823:Taxoids; D000077143:Docetaxel; D004961:Estramustine; D008942:Mitoxantrone; D017430:Prostate-Specific Antigen; D011241:Prednisone