Weekly docetaxel and zoledronic acid every 4 weeks in hormone-refractory prostate cancer patients.
OBJECTIVE
To investigate the safety and efficacy of docetaxel and zoledronic acid in patients with hormone-refractory prostate cancer (HRPC), based on preclinical evidence of synergism between taxanes and bisphosphonates.


METHODS
Twenty-five patients with advanced HRPC received weekly docetaxel 30 mg/m2: in 18 patients with symptomatic bone metastases and normal renal function, docetaxel was combined with zoledronic acid, 4 mg i.v. every 4 weeks. Premedication consisted of intravenous dexamethasone before docetaxel. No oral steroids were given.


RESULTS
Overall, 12 patients (48%) had a PSA response (reduction of 50% or more compared to baseline). A PSA response was achieved in 8/18 patients (44%) receiving concomitant docetaxel and zoledronic acid, and in 7/12 patients (58%) receiving docetaxel and zoledronic acid as first-line therapy. The weekly schedule of docetaxel resulted in a mean received dose intensity of 26 mg/m2/week, or 87% of the planned dose intensity. Toxicity was mild and as expected for docetaxel. The median time to progression was 7 months, and the median overall survival was 16 months.


CONCLUSIONS
Concomitant treatment with docetaxel and zoledronic acid is safe and has encouraging activity in HRPC. The combination should be evaluated in randomised clinical trials.
Singleton Hospital, South West Wales Cancer Institute, Sketty, Swansea, SA2 8QA, UK. gianfilippo.bertelli@swansea-tr.wales.nhs.uk
Gianfilippo
G
Bertelli
Abdelhamid
A
Heouaine
Giuseppe
G
Arena
Ambrogio
A
Botto
Ornella
O
Garrone
Ida
I
Colantonio
Marcella
M
Occelli
Elena
E
Fea
Silvia
S
Giubergia
Marco
M
Merlano
D000368:Aged; D000728:Androgens / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077211:Zoledronic Acid
D000728:Androgens; D004164:Diphosphonates; D007093:Imidazoles; D043823:Taxoids; D000077143:Docetaxel; D000077211:Zoledronic Acid; D017430:Prostate-Specific Antigen