Imatinib mesylate and zoledronic acid in androgen-independent prostate cancer.
OBJECTIVE
To determine the safety and efficacy of zoledronic acid (Zometa) combined with imatinib mesylate (Gleevec) in patients with bone pain due to androgen-independent prostate cancer.


METHODS
Fifteen patients were treated with zoledronic acid 4 mg intravenously every 28 days and imatinib mesylate 400 mg/day. The pain response, defined as a 2-point reduction in the Present Pain Intensity Scale or normalization if the initial score was 1, was the primary endpoint. Secondary endpoints included palliative response, prostate-specific antigen response, measurable disease response, time to progression, impact on quality of life, decrease in markers of bone turnover, and tolerability of the drug combination.


RESULTS
The study was stopped early because of a lack of activity. No palliative or clinical activity was detected for the combination, and no prostate-specific antigen responses were observed. The median time to progression was 4 weeks (95% confidence interval 3 to 5), and the median duration of treatment was 8 weeks (range 1.6 to 16.7). The median overall survival was 54 weeks (95% confidence interval 18 to 90). Therapy was associated with a reduction in urine N-telopeptides and a trend toward a reduction in serum osteocalcin, but no change occurred in bone-specific alkaline phosphatase.


CONCLUSIONS
In this patient population, imatinib mesylate and zoledronic acid produced no prostate-specific antigen responses and had no palliative or clinical activity.
Tiffany
N M
NM
Division of Hematology and Medical Oncology, Oregon Health and Science University and Portland Veterans Affairs Medical Center, Oregon, Portland 97239, USA.
Wersinger
E M
EM
Garzotto
M
M
Beer
T M
TM
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D001847:Bone Diseases / Q000188:drug therapy* / Q000209:etiology; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D006801:Humans; D000068877:Imatinib Mesylate; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D001549:Benzamides; D004164:Diphosphonates; D007093:Imidazoles; D010879:Piperazines; D011743:Pyrimidines; D000077211:Zoledronic Acid; D000068877:Imatinib Mesylate; D017430:Prostate-Specific Antigen