Bone-targeted therapy: phase II study of strontium-89 in combination with alternating weekly chemohormonal therapies for patients with advanced androgen-independent prostate cancer.
OBJECTIVE
Bone-targeted therapy that combines strontium-89 (Sr-89) with alternating weekly chemohormonal therapy may improve clinical outcomes in patients with metastatic hormone-refractory prostate cancer. This phase II study investigated the addition of Sr-89 to an alternating weekly regimen of doxorubicin and ketoconazole with paclitaxel and estramustine in patients with progressive prostate cancer and bone involvement.


METHODS
Twenty-nine patients with progressive adenocarcinoma of the prostate and osteoblastic bone metastases who failed conventional hormonal therapy were registered for the study. Of those, 27 were treated with Sr-89 on day 1 of week 1. On weeks 1, 3, and 5, patients received doxorubicin (20 mg/m on day 1) and oral ketoconazole (400 mg 3 times a day for 7 days). On weeks 2, 4, and 6, patients received paclitaxel (100 mg/m(2)) and oral estramustine (280 mg 3 times a day for 7 days). No treatment was given during weeks 7 and 8. Cycles were repeated every 8 weeks.


RESULTS
A > or =50% reduction in prostate-specific antigen level was maintained for at least 8 weeks in 77.7% of the patients (21 patients) at 16 weeks and in 66.6% (18 patients) at 32 weeks. The median progression-free survival was 11.27 months (range, 1.83-29.53), and the median overall survival was 22.67 months (1.83-57.73+). Two patients died during study because of disease progression. Overall, the chemotherapy combined with Sr-89 was well tolerated.


CONCLUSIONS
Our results demonstrate that the combination of alternating weekly chemohormonal therapies with Sr-89 demonstrates a prolonged progression-free and overall survival with acceptable toxicity. Further investigation of combination therapies with Sr-89 is warranted.
Amato
Robert J
RJ
The Methodist Hospital, The Methodist Hospital Research Institute, Genitourinary Oncology Program, Houston, TX 77030, USA. ramato@tmhs.org
Hernandez-McClain
Joan
J
Henary
Haby
H
D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D004961:Estramustine / Q000008:administration & dosage; D006801:Humans; D007654:Ketoconazole / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D013326:Strontium Radioisotopes / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
D000935:Antifungal Agents; D013326:Strontium Radioisotopes; D004961:Estramustine; D004317:Doxorubicin; D017430:Prostate-Specific Antigen; D017239:Paclitaxel; D007654:Ketoconazole