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Bisphosphonate Therapy for Patients with Osteolytic and Osteoblastic Bone Metastases from Breast or Prostate Cancer (pp. 157-180) $25.00
Authors:  Allan Lipton (Milton S. Hershey Medical Center, Hershey, PA)
The majority of patients with advanced breast or prostate cancer will develop painful and debilitating bone metastases that are typically described based on their radiographic appearance as either osteolytic or osteoblastic. Bone metastases associated with breast cancer often have a mixed radiologic appearance, and bone metastases in patients with prostate cancer are typically osteoblastic.
As a result of excessive bone resorption, patients with bone metastases are at significant risk for developing skeletal complications, including severe bone pain, pathologic fractures, spinal cord compression, and hypercalcemia. Supportive interventions include administration of bisphosphonates, radiation therapy, surgery, and analgesics. Since the mid 1990s, intravenous pamidronate (90 mg) has been the international standard for the treatment of osteolytic bone lesions in patients with breast cancer and multiple myeloma based on evidence that it significantly reduces skeletal morbidity compared with placebo. Zoledronic acid was subsequently developed and was compared with pamidronate in 1,648 patients with breast cancer and multiple myeloma. The results of this large, randomized trial demonstrated that 4 mg zoledronic acid (via a convenient 15-minute infusion) was as safe as 90 mg pamidronate (via 2 hour infusion), and a preplanned multiple event analysis showed that zoledronic acid significantly reduced the risk of skeletal complications compared with pamidronate. Importantly, patients with breast cancer enrolled in this trial had all types of bone lesions, from osteolytic to osteoblastic. Based on these results, 4 mg zoledronic acid is rapidly becoming the new international standard in patients with bone metastases from breast cancer. Intravenous pamidronate and zoledronic acid are the only bisphosphonates recommended by the American Society of Clinical Oncology.
Although the majority of bisphosphonate studies in patients with solid tumors have focused on breast cancer, there is a need for effective therapy for bone metastases associated with prostate cancer. However, randomized, placebo-controlled trials with clodronate and pamidronate in patients with advanced prostate cancer failed to demonstrate significant palliation of bone pain or reduction in skeletal complications. In contrast, in a recent randomized, placebo-controlled trial, 4 mg zoledronic acid significantly reduced the occurrence of skeletal complications and provided long-term palliation of bone pain in patients with advanced prostate cancer. Therefore, zoledronic acid is the only bisphosphonate to demonstrate efficacy in both osteolytic and osteoblastic disease. With the availability of newer generation, highly potent agents such as zoledronic acid, the role of bisphosphonates in the treatment of malignant bone disease continues to evolve. 

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Bisphosphonate Therapy for Patients with Osteolytic and Osteoblastic Bone Metastases from Breast or Prostate Cancer (pp. 157-180)