The systemic treatment of bone metastases.

Bone metastases are a major source of morbidity in patients with metastatic cancer. There are effective systemic treatments available for patients with breast and prostate cancers, who are the majority of patients with bone metastases. Unfortunately, < 50% of patients benefit from currently available endocrine or cytotoxic chemotherapy, although problems of response assessment often lead to under reporting of true response rates. A better understanding of the mechanisms underlying the development of osteolytic bone metastases and the crucial role of increased osteoclastic activation provided the rationale for the use of the bisphosphonates. They reduce hypercalcemic episodes, pain, and pathologic fractures, and can induce radiologic healing of skeletal metastases. The development of potent, easily tolerated oral preparations will lead to their increased use by patients with osteolytic bone metastases. Radioisotopes used either alone or with external beam radiotherapy are effective in palliating the pain of skeletal metastases in patients with breast and prostate cancer and result in little associated subjective toxicity. Most studies have lacked placebo-treated controls, and the results of multicenter studies evaluating the benefits of radioisotopes with respect to pain relief and quality of life are awaited. These treatments combined with local treatments such as radiotherapy, surgery, and analgesia can provide effective palliation of symptoms for the majority of patients.