Bisphosphonates, a class of drugs used to alleviate the pain and other complications associated with cancer that has spread to bones, appear to be safe and effective when patients take them for more than two years, according to a report in a recent issue of the Journal of Clinical Oncology (Vol. 19, No. 14: 3434-3437).

Bisphosphonates can help decrease the risk of pain and fractures when cancer has spread to bone tissue, but whether these drugs are safe and effective when taken for more than two years has not been previously established.

Researchers, led by Allan Lipton, MD, at the Pennsylvania State University School of Medicine in Hershey, studied 17 women with advanced breast cancer and five men with multiple myeloma. All the participants in the study had cancer that had spread to their bones.

Bisphosphonates are known to reduce the rate of ‘bone turnover,’ a naturally occurring process that maintains a balance between breaking down and building up tiny areas of each bone. By reducing the rate of turnover, these drugs are thought to make the bones stronger, making fractures less likely when subjected to the stress of bone metastases.

Two earlier studies looking at the effectiveness of pamidronate for up to two years found that the drug was able to reduce the number of skeletal complications by about 30% in patients, compared to in those who took an inactive placebo.

In the current study, each patient received one of two bisphosphonate drugs, either pamidronate or zoledronic acid, for an average of about three and a half years.

Lipton and his colleagues found that the fracture rate beyond two years was no greater than during the first two years of treatment, and no stress fractures occurred in the long (arm and leg) bones during prolonged therapy.

Perhaps more importantly, prolonged treatment with bisphosphonates also appeared to be safe. About half the patients remained on therapy at the end of the study, while most of the others stopped only because the treatment no longer appeared to be effective. The drugs did not cause any significant changes in blood counts or other laboratory tests. “Prolonged therapy was well tolerated,” the researchers conclude.

One of the study authors, Francisco J. Esteva, MD, PhD, with the University of Texas, M. D. Anderson Cancer Center in Houston, points out that bisphosphonates are an important advance in the supportive care of patients with metastatic cancer.

“These agents are safe and effective in a variety of settings,” Esteva says. “The most important indications for their use are the treatment of hypercalcemia (high calcium levels in the blood) and bone metastases.”

But although bisphosphonates are generally well tolerated, Esteva notes that occasionally patients develop side effects such as “reactions at the injection site, difficulty breathing, low calcium levels, and lack of appetite.”

But “most patients with cancer that is metastatic to the bone derive benefit from long-term use of bisphosphonates,” he adds.

Herman Kattlove, MD, a medical oncologist and medical editor with the American Cancer Society (ACS) points out that the main weakness of this study is that the number of patients was low.

“Many drugs will have side effects in a small percentage of people, and this study may not have been large enough to detect them, so I would like to see results on more patients,” Kattlove says.

But he adds, “these patients can have severe bone pain and fractures, both of which are partly alleviated by bisphosphonates. The benefit far outweighs any risk in these patients, of whom the great majority will die from their disease.”

“I would absolutely recommend bisphosphonate therapy for life in any patient with significant bone involvement with cancer,” Kattlove concludes.