In a recent study, treatment with Zometa ^[1] (zoledronic acid) increased overall and progression-free survival rates among multiple myeloma patients compared to Bonefos (clodronate). Additionally, Zometa was more effective in preventing bone loss and fractures. The results were presented June 6 at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago by Dr. Gareth Morgan of the Royal Marsden Hospital in London.

Bone is in a constant balance of being broken down and being replenished. A perfect balance keeps a person’s bones strong. However, in multiple myeloma patients, this balance is disrupted, and bone is broken down faster than it is rebuilt, resulting in weaker, more easily broken bones.

Zometa and Bonefos are both bisphosphonates, which reduce bone loss and fractures by helping to rebuild bone. Zometa is approved for use in the United States; however, Bonefos is not.

Previous pre-clinical and clinical trials have suggested that in addition to preventing bone loss and related complications, Zometa may also have anti-cancer effects. However, no clinical trials have shown that Zometa has anti-myeloma effects. Dr. Morgan suggested during his presentation that Zometa may reduce tumor growth, cause death of myeloma cells, and stimulate the immune system.

Given the results of these past trials, Dr. Morgan and his colleagues evaluated Zometa as an anti-myeloma agent in comparison to Bonefos by comparing the effect the two drugs have on overall survival and progression-free survival in myeloma patients. They also evaluated the drugs’ effects on bone-related complications.

Almost 2,000 newly diagnosed multiple myeloma patients, 70 percent of whom had bone disease, participated in the study. Each participant received either Zometa or Bonefos, in addition to the myeloma therapies they were receiving. At the time of the ASCO presentation, 75 percent of participants had stayed on their bisphosphonate until disease progression, while 25 percent discontinued their bone treatment once their myeloma was stable or in remission.

“Zometa is superior to Bonefos in the prevention of skeletal-related events in patients with newly diagnosed myeloma,” said Dr. Morgan. Twenty-seven percent of the patients receiving Zometa experienced skeletal-related complications, compared to 35 percent of the Bonefos group.

Survival rates were also higher among patients receiving Zometa. Overall survival was 50 months for the Zometa group and 44.5 months for the Bonefos group. Progression-free survival was 19.5 months for the Zometa group and 17.5 months for the Bonefos group. According to Dr. Morgan, a survival advantage of 5.5 months is “clinically significant.”

Side effects were minimal for both treatments, and there was no difference in kidney function deterioration among the Bonefos and Zometa groups. However, the rate of osteonecrosis of the jaw, a condition in which there is a loss of blood supply to the jaw resulting in jawbone death, was higher in the Zometa group (3.5 percent) compared to the Bonefos group (0.3 percent).

During his presentation, Dr. Morgan posited an important question regarding Zometa’s effectiveness in improving survival: “Is the [survival benefit] because of an anti-myeloma effect or because of the effect of reducing skeletal-related events?”

Analysis of the results showed that there was no relationship between a reduction in skeletal-related events and patient survival. Additionally, patients without myeloma bone disease experienced a survival benefit when treated with Zometa. Therefore, it was concluded that Zometa must have inherent anti-cancer effects of its own.

In regard to treating myeloma bone disease, Dr. Morgan concluded, “[Zometa] is the new standard of care for patients with myeloma.”

However there are still many questions about the use of Zometa that physicians seek to answer: For which patients does Zometa provide a survival benefit? In particular, do patients in complete remission benefit from continued Zometa treatment? What is the optimal duration of treatment?

For more information, please refer to abstract 8021 ^[2] on the ASCO meeting ^[3] website and related Beacon ^[4] news about recent advances in treating myeloma bone disease.