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Low Doses of Zoledronic Acid Reduce Complications of Bone Metastases

Low Doses of Zoledronic Acid Reduce Complications of Bone Metastases

Researchers at Cedars-Sinai Medical Center report that very low doses of a potent new bisphosphonate, zoledronic acid (Zometa), reduces the complications arising from multiple myeloma and breast cancer that have metastasized to the bone. The study, published in Cancer (91[7]:1191-1200), shows that a 5-minute infusion of zoledronic acid has the same effect as much higher doses of pamidronate (Aredia), a similar therapy administered over a 2-hour period.

"Not only was zoledronic acid effective in much lower doses, but we could give the drug to patients over a much shorter time than we could with pamidronate," said James Berenson, md, director of the Multiple Myeloma and Bone Metastases Program at Cedars-Sinai Medical Center. "This means a more potent and convenient alternative for patients battling the debilitating effects of cancers that have spread to the bone."

Bisphosphonates vs Radiation

Both zoledronic acid and pamidronate are types of bisphosphonates—compounds that work by slowing the production of cells that destroy bone. Under normal conditions, cells called osteoclasts remove old bone, after which cells called osteoblasts can begin building new bone. But when cancer spreads, the normal balance of the cells is disturbed and the osteoclasts are more active, causing bone fractures, pain, spinal cord compression, and hypercalcemia.

Radiation therapy is often required to help alleviate these complications. However, radiation causes side effects such as extreme fatigue and lower levels of infection-fighting white blood cells. Alternatively, bisphosphonates cause fewer and less serious side effects, which include flu-like symptoms and some bone pain, and can be given safely to patients receiving simultaneous chemotherapy or hormonal therapy. Thus, pamidronate and other bisphosphonates have been increasingly used for skeletal complications due to cancers that have spread.

Zoledronic Acid vs Pamidronate

Earlier studies by Dr. Berenson and his colleagues have already shown that a lower dose of zoledronic acid is safe and reduces the indicators of bone loss, such as excess calcium in patients whose cancer had spread to the bone. The purpose of this current study is to determine whether zoledronic acid is as effective as pamidronate in reducing bone complications.

Investigators evaluated 280 patients with bone metastases due to metastatic breast cancer or multiple myeloma. Those who received zoledronic acid were split into three groups by dosage, either 0.4, 2.0, or 4.0 mg, infused over 5 minutes. Another group of patients received 90 mg of pamidronate infused over 2 hours. Both drugs were administered once a month for 10 months. The treatment was considered effective if fewer than 30% of the group required radiation therapy to the bone. Although some patients discontinued treatment due to death or complications from their cancer, approximately 76% of all patients given zoledronic acid and 82% in the pamidronate group completed at least 6 months of the study.

Radiation-Reducing Doses

The results show that zoledronic acid was as effective as the much higher dose of pamidronate in reducing the need for radiation to bone. In the 2.0-mg and 4.0-mg zoledronic acid groups respectively, 19% and 21% of patients received radiation; 18% of patients in the pamidronate arm also received radiation. The lowest dose (0.4 mg) of zoledronic acid was found to be significantly less effective than either the higher doses of zoledronic acid or pamidronate, with 24% receiving radiation.

"We found that the proportion of patients receiving radiation to bone in the zoledronic acid group was very comparable to those patients receiving the much higher dose of pamidronate," added Dr. Berenson. "Complications such as fractures, spinal cord compression…and hypercalcemia occurred less frequently in the patients receiving the higher doses of zoledronic acid."

In addition, investigators found that the higher doses of zoledronic acid increased bone density in the spine by almost 10%. "Zoledronic acid may provide a much more convenient and effective therapy for overcoming the skeletal complications of bone metastases," said Dr. Berenson.

Currently, Dr. Berenson and his team are conducting phase III clinical trials to further compare the effects of zoledronic acid and pamidronate in bone metastases.

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