When cancer spreads to bone during the advanced stages of disease, the results can be devastating. Some patients experience severe pain and face an increased risk of fractures and other skeletal-related complications. These often require additional treatments and may further diminish a patient's quality of life and compromise survival.

As systemic anticancer therapies improve, the problem of bone metastases is likely to become increasingly common, and new, cost-effective therapies are needed. Toward this end, a strategy aimed at preventing or delaying skeletal-related complications from bone metastases is being evaluated in a prospective, randomized NCI-sponsored clinical trial.

The researchers are testing whether a drug called zoledronic acid (Zometa), a standard therapy for patients with bone metastases, is more effective when given with a radiopharmaceutical such as strontium-89 or samarium-153. Radiopharmaceuticals are bone-seeking radioactive agents that incorporate into areas of bone being turned over by metastases.

The beauty of radioisotopes, which are administered intravenously, is that they target all bone metastases with a low concentration of radiation in the surrounding normal bone marrow and other structures, according to the researchers.

"If a patient has 30 to 40 spots on an affected bone, the radioisotope would go to all of the sites," said co-principal investigator Dr. Michael J. Seider of Summa Health System Hospitals in Akron, OH. "It is a fast, simple, and relatively non-toxic drug."

The trial, Dr. Seider noted, is asking a simple question: "If we add a radioisotope to a drug that already works in delaying skeletal-related events, will we further delay these skeletal-related events?"

The randomized, phase III study is enrolling patients with three cancers that commonly spread to bone - lung, breast, and prostate. To enroll in the study, participants must have bone metastases but no significant bone pain. All participants will receive zoledronic acid as a primary treatment and half will receive a single dose of a radioisotope. (The trial presumes that either radioisotope is acceptable for treatment.)

Participants will be followed for the development of pain and skeletal-related complications. During the trial, patients may receive any other type of therapy, including cytotoxic therapy, hormone therapy, or additional radiation therapy (except for treatment of bone metastases).

This point is critical because there is a misperception, particularly among some medical oncologists, that patients taking radioisotopes cannot receive other therapies at the same time. Studies have shown, however, that radioisotopes can be given with other therapies without causing more side effects than other combination therapies.

"We need to debunk the misconceptions and fears that exist regarding radiopharmaceuticals," said co-lead investigator Dr. Corey Langer of the Fox Chase Cancer Center. "The big problem with this class of drugs is the false impression that once you give them to patients their marrow function never recovers. We certainly are not seeing that in this trial."

To date, the trial has enrolled more than 50 of a planned 352 participants. It includes a component that will measure quality of life. Another question is the cost effectiveness of the combination therapy, because delaying the need for additional treatments for skeletal-related events could prevent expensive procedures.

If the trial is successful, noted Dr. Langer, the combination therapy could improve the lives of many patients with bone metastases by minimizing their pain and delaying further complications.

The current challenge is to overcome the notion that giving radioisotopes would prevent patients from getting any other type of therapy. "If we can break through this misconception, the study looks to be very promising," said Dr. Seider.

—Edward R. Winstead