Docetaxel, low-dose estramustine, and doxifluridine in hormone-refractory metastatic prostate cancer.
OBJECTIVE
Advanced prostate cancer, which is one of the most common cancers, usually progresses to hormone-refractory prostate cancer (HRPC). A recent randomized trial of treatment with docetaxel demonstrated improved survival for patients with HRPC. The combination of docetaxel and estramustine phosphate (estramustine) has been reported to be effective for HRPC. Low-dose estramustine suppresses the pituitary-gonadal axis. Docetaxel plus 5-fluoro-5'-deoxyuridine (5'-dFUrd) had supra-additive cytotoxic effects on HRPC cells consistent with the molecular mechanism. Therefore, we examined the efficacy of adding 5'-dFUrd on the chemotherapy regimen, which consist docetaxel and estramustine.


METHODS
All of the HRPC patients were treated with estramustine 140 mg orally twice 5'-dFUrd 200 mg orally four times daily on days 1-21, and docetaxel 60 mg/m(2) was administered on day 1. We evaluated serum prostate-specific antigen (PSA) and measurable responses, the progression-free and overall survival, and the impact on adverse effects and the quality of life (QOL).


RESULTS
Of 34 patients with a median age of 72.3 years, 73% showed PSA responses and 70% showed measurable responses. The median progression-free survival was 18.0 and 5.8 months for PSA responders and non-responders and the overall survival was 19.4 months, respectively. There were few serious adverse effects. Grade 3/4 neutropenia occurred in 32.4% of the patients, and was easily managed with granulocyte colony-stimulating factor (G-CSF) injection. There was no significant change in the overall QOL scores serially.


CONCLUSIONS
This study shows that the combined regimen is tolerable and effective in Japanese HRPC patients.
Wada
Yoshihiro
Y
Department of Urology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto, 860-8556, Japan. pullpullachan326@bridge.ocn.ne.jp
Kikuchi
Ken
K
Takahashi
Wataru
W
Honda
Jiro
J
Nakanishi
Juro
J
Matsumoto
Koichiro
K
Kuwahara
Tomohiro
T
Kai
Nobuyuki
N
Kikukawa
Hiroaki
H
Ueda
Shoichi
S
D000230:Adenocarcinoma / Q000188:drug therapy*; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D000077143:Docetaxel; D004961:Estramustine / Q000008:administration & dosage; D005467:Floxuridine / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017430:Prostate-Specific Antigen / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011788:Quality of Life; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
D043823:Taxoids; D005467:Floxuridine; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D004961:Estramustine; D017430:Prostate-Specific Antigen; C025034:doxifluridine