Bisphosphonates: Clinical Experience

Abstract

Learning Objectives: After completing this course, the reader will be able to: Explain the importance of bone disease in the common solid tumors of adulthood. Describe the pathophysiology of bone metastasis. List the specialized end points used in clinical trials assessing treatment of bone disease. Discuss the current standard for the treatment and prevention of bone complications that may arise in cancer and its treatment. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com Bone is a preferred site of metastasis for many solid tumors, and the complications associated with bone metastases can result in significant skeletal morbidity including severe bone pain, pathologic fracture, spinal cord compression, and hypercalcemia of malignancy (HCM). Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletal-related event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and HCM. Bisphosphonates have been shown to significantly reduce the incidence of these events in patients with bone metastases. Zoledronic acid (Zometa®; Novartis Pharmaceuticals Corp.; East Hanover, NJ), pamidronate (Aredia®; Novartis Pharmaceuticals Corp.), clodronate (Bonefos®; Anthra Pharmaceuticals; Princeton, NJ), and ibandronate (Bondronat®; Hoffmann-La Roche Inc.; Nutley, NJ) all have demonstrated efficacy superior to that of placebo in patients with breast cancer. Zoledronic acid is the only bisphosphonate that has been compared directly with pamidronate, and it was shown by multiple event analysis to be significantly more effective at reducing the risk of an SRE. In patients with prostate cancer, clodronate, etidronate (Didronel®; Procter and Gamble Pharmaceuticals, Inc.; Cincinnati, OH), and pamidronate have demonstrated transient palliation of bone pain. However, zoledronic acid is the only bisphosphonate to demonstrate both significant and sustained pain reduction and a significantly lower incidence and longer time to onset of SREs compared with placebo. Zoledronic acid is also the only bisphosphonate to demonstrate efficacy in patients with bone metastases from a variety of other solid tumors, including lung cancer and renal cell carcinoma. In conclusion, bisphosphonates effectively reduce skeletal complications in patients with bone metastases from breast cancer, and zoledronic acid has demonstrated the broadest clinical activity in patients with a wide variety of tumor types.