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Bisphosphonates and Other Bone-Targeting Compounds in the Treatment of Cancer
Decision Resources, Inc, Dec 2005, Pages: 13
Bisphosphonates have been in use for approximately 25 years, most commonly to treat diseases characterized by bone loss, such as osteoporosis. Bisphosphonates are also used in adjunctive treatment of cancers that involve bone-related complications. Currently, bisphosphonates are approved only for the treatment of patients with advanced cancer who have bone metastases, but researchers are investigating the direct antitumor effects of these agents and their benefits in treating bone loss resulting from hormonal cancer treatment.
In this report, we present an overview of bisphosphonate treatment, including a description of bone remodeling, currently available agents, and safety concerns. We discuss the use of bisphosphonates in the treatment of bone metastases and bone loss in breast and prostate cancer patients and as antitumor agents. We also profile emerging nonbisphosphonate agents that target bone and may pose significant competition for bisphosphonates.
Business Implications
- Intravenous (IV) treatment with bisphosphonates such as pamidronate (Novartis's Aredia) and zoledronic acid (Novartis's Zometa), in conjunction with standard chemotherapy, has become the standard of care for patients with bone lesions due to multiple myeloma and for patients with solid tumors who have bone metastases. These agents are used to reduce the incidence of bone-metastasis-related exacerbations such as bone pain, fractures, and spinal cord compression.
- A major new potential market segment for bisphosphonates in oncology is the prevention of bone loss in patients with early-stage breast and prostate cancer who are being treated with hormonal therapies. Hormonal therapies pose the risk of rapid and severe bone loss. Currently, the most efficacious treatment appears to be zoledronic acid, and several Phase III trials of IV zoledronic acid are ongoing in these patient populations.
- The direct antitumor effects of bisphosphonates and their clinical significance (e.g., in reducing tumor burden and improving patient survival) are controversial. Several in vitro studies, primarily in cultured breast and prostate cancer cell lines, have demonstrated that bisphosphonates inhibit tumor cell proliferation and induce apoptosis. In addition, combinations of nitrogen-containing bisphosphonates with various standard anticancer agents have demonstrated synergistic antitumor effects. Several large clinical trials that are designed to determine the efficacy of bisphosphonates as antitumor agents are ongoing in the United States and Europe.
- Some pharmaceutical companies are developing nonbisphosphonate bone-targeting compounds for use in oncology treatments. Amgen is developing a monoclonal antibody (MAb) drug, denosumab, for bone loss in postmenopausal osteoporosis and in oncology indications; Ariad is developing nonbisphosphonate compounds that target both bone and the mammalian target of rapamycin (mTOR), a signaling kinase that is central to disease pathways in many types of cancer. Ariad's compounds are in the preclinical stage, so they have yet to achieve proof of principle in humans. However, compounds that localize in bone and specifically target cancer pathways may have a greater potential for antitumor efficacy than the bisphosphonates.
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