乳がん患者においてゾレドロン酸の投与頻度を減少させても安全である（Abstract: LBA9003）

New findings from a phase III randomized study, OPTIMIZE-2, suggest that after a year of monthly treatment with zoledronic acid, women with breast cancer and bone metastasis can safely scale back treatment to an every-three-month schedule. Lower-frequency dosing appeared to have comparable efficacy in reducing complications from bone metastases as monthly dosing, and may decrease the risk of rare, serious side effects associated with zoledronic acid.

"The addition of bisphosphonate drugs like zoledronic acid has dramatically improved the care of patients with bone metastases. But long-term treatment carries the risk of serious side effects, such as osteonecrosis of the jaw and kidney problems," said lead study author Gabriel N. Hortobagyi, M.D., a professor of medicine at the M.D. Anderson Cancer Center in Houston, TX. "We found that less frequent treatment may reduce the risk of serious side effects, with added benefits in reduced patient inconvenience and cost."

Zoledronic acid is commonly used to reduce complications from bone metastases, such as bone fractures and spinal cord compression. Most doctors give zoledronic acid every four weeks for the first year, starting at diagnosis of bone metastases. It is thought that the treatment should continue indefinitely, but doctors have been concerned about the risk of side effects. To date, there has been limited research, and there are no evidence-based guidelines for the optimal treatment schedule after the first year.

In the OPTIMIZE-2 study, 403 women with bone metastases from breast cancer who had completed roughly one year of monthly zoledronic acid therapy were randomly assigned to receive zoledronic acid every month vs. every three months for an additional year. Researchers assessed the skeletal event rate (fractures of long bones and vertebrae, spinal cord compressions, and interventions precipitated by bone metastases).

The skeletal event rates were comparable between the two arms (22 percent in the monthly arm vs. 23.2 percent in the every-three-months arm) indicating that less frequent treatment was not inferior to monthly treatment. Other efficacy measures, such as time to first skeletal event and bone turnover markers, were also similar between the two arms. There were no differences in pain levels and use of pain medications between the two treatment schedules. However, due to design limitations and statistical concerns, the efficacy data of OPTIMIZE-2 should be interpreted with caution.

No obvious differences in overall safety profile and in kidney side effects were noted between the two zoledronic acid treatment regimens. Two cases of osteonecrosis of the jaw were reported in the monthly arm, whereas none in the every-three-months treatment arm.

"Women with metastatic breast cancer who require long-term protection against bone fractures now have the option of receiving maintenance bisphosphonate therapy at less frequent intervals without compromising benefit or safety," said Patricia Ganz, M.D., FASCO, ASCO Expert.

This research was supported by Novartis Pharmaceuticals.