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Bone-Targeted Therapy

Phase II Study of Strontium-89 in Combination With Alternating Weekly Chemohormonal Therapies for Patients With Advanced Androgen-Independent Prostate Cancer

Amato, Robert J., DO; Hernandez-McClain, Joan, MPH; Henary, Haby, MD

American Journal of Clinical Oncology: December 2008 - Volume 31 - Issue 6 - p 532-538
doi: 10.1097/COC.0b013e318172aa92
Original Article: Genitourinary

Objectives: 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/m2 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/m2) 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 ≥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.

From The Methodist Hospital, The Methodist Hospital Research Institute, Genitourinary Oncology Program, Houston, Texas.

Reprints: Robert J. Amato, DO, The Methodist Hospital, The Methodist Hospital Research Institute, Genitourinary Oncology Program, 6560 Fannin Street, Suite 2050, Houston, TX 77030. E-mail:

© 2008 Lippincott Williams & Wilkins, Inc.