Docetaxel and zoledronic acid in patients with metastatic hormone-refractory prostate cancer.
OBJECTIVE
To evaluate the safety and efficacy of combined docetaxel-zoledronic acid treatment in patients with metastatic hormone-refractory prostate cancer (HRPC), as bisphosphonates are reported have a synergistic antitumoral effect when combined with taxanes.


METHODS
Between January 2001 and June 2003, 14 patients with HRPC were treated; their mean (range) age was 71 (57-86) years and mean prostate-specific antigen (PSA) level 202 (6-489) ng/mL. Five patients had had previous chemotherapy (cyclophosphamide in two, mitoxantrone-prednisolone in three). The response criteria were the Karnofsky performance status, a positive response in mean daily analgesic consumption (defined as a decrease by more than half), decreased serum PSA (by more than half) at 8 weeks, blood transfusion, bone scan at 6 months, skeletal-related events and survival.


RESULTS
Patients received a mean (range) of 7.3 (6-10) cycles of therapy; there was no reported drug-related toxicity and all patients stayed at home for their treatment. Only three patients required a blood transfusion and no bone fractures were reported. At 2 months, six patients requiring analgesic drugs decreased their consumption by more than half (anti-inflammatory, paracetamol, narcotics) and eight had a reduction in PSA by more than half; of these eight with a PSA response at 2 months, six had biochemical progression with a mean delay of 6.2 (3-11) months. At 6 months, five patients had disease progression on bone scan. Nine patients had chemo-naïve hormone-refractory prostate cancer; three had biochemical progression at 2 months and two of these had progression on their bone scan. Two patients died at 7 and 15 months of follow-up; the mean follow-up was 10.2 (6-15) months. Using Kaplan-Meier plots, biochemical progression-free survivals were five of 14 at 6 months and two of 14 at 12 months; overall survival was 12 of 14 at 6 and 12 months.


CONCLUSIONS
Docetaxel-zoledronic acid therapy is safe and decreased the serum PSA by more than half at 2 months in more than half the patients. Prospective randomized trials are needed to assess this new approach.
Department of Urology, CHU Henri Mondor, Assistance Publique des Hôpitaux de Paris, Créteil, France.
Dimitri
D
Vordos
Bernard
B
Paule
Francis
F
Vacherot
Yves
Y
Allory
Laurent
L
Salomon
Andras
A
Hoznek
René
R
Yiou
Dominique
D
Chopin
Claude Clément
CC
Abbou
Alexandre
A
de la Taille
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D004164:Diphosphonates / Q000008:administration & dosage; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D018931:Antineoplastic Agents, Hormonal; D004164:Diphosphonates; D007093:Imidazoles; D043823:Taxoids; D000077143:Docetaxel; D000077211:Zoledronic Acid