The results from a clinical trial, called the ZMAX trial, suggest that administering Zometa intravenously over a longer period does not increase the drug’s safety compared to shorter infusion times.

Dr. James Berenson, from Berenson Oncology and lead author of the study, stated in email correspondence with The Myeloma Beacon that he hopes these study results will reassure patients that a 15-minute infusion time is safe.  Ultimately, the study authors suggested that infusion duration should be based on individual patient considerations.

Zometa ^[1] (zoledronic acid) is an intravenous bisphosphonate that reduces bone loss and fractures by inhibiting the cells that breakdown bone. Studies have also explored its potential anti-cancer effects (see related Beacon ^[2] news).

Treatment of myeloma bone disease is important, since 20 percent of multiple myeloma patients experience a fracture at the time of their myeloma diagnosis, and 60 percent of multiple myeloma patients experience a fracture during their cancer.

Since Zometa is primarily excreted from the body through the kidneys, it and other bisphosphonates can lead to an increased risk of kidney damage.  Furthermore, due to the nature of the disease, multiple myeloma patients are at increased risk of kidney failure compared to the general population (see related Beacon ^[3] news). Approximately 20 percent of all myeloma patients will develop progressive kidney failure sometime during the course of their disease.

Therefore, researchers sought to determine in this study if kidney damage could be minimized in patients receiving intravenous Zometa by slowing the rate at which the drug is administered.  This, they hypothesized, would lower the levels of the drug in the patient’s bloodstream, thus lowering its accumulation in the kidneys.

A total of 176 multiple myeloma patients were treated in centers across the United States.  Patients were randomly assigned to receive 4 mg Zometa intravenously over a 15-minute or 30-minute time period.  Tests were then conducted to measure the amount of Zometa that accumulated in the blood following treatment as well as chemicals released from the kidney that indicate damage.

As researchers expected, the amount of Zometa in the bloodstream was higher at the end of the treatment period for patients who received their dose in 15 minutes as opposed to 30 minutes, 249 ng/mL compared to 172 ng/mL, respectively.

After one year of treatment, slightly fewer patients in the 30-minute treatment group had measurable kidney damage compared to the 15-minute treatment group, 16 percent versus 20 percent, respectively.  The differences were not, however, statistically significant.

When tests were performed after two years of treatment, researchers found no difference in the percent of patients experiencing kidney damage in the two treatment groups (28 percent for the 15-minute group and 27 percent for the 30-minute group).

The same side effects were experienced in both treatment groups, the most common of which were skeletal-related events and osteonecrosis of the jaw, a condition that is associated with a loss of blood supply to the jaw resulting in jawbone death.

The researchers noted that since the time of their study, the U.S. Food and Drug Administration has recommended a decreased dose of Zometa be administered to multiple myeloma patients based on the severity of existing kidney damage.  The researcers suggested that further studies should be conducted with a larger patient group to determine the effects of increased administration time with the new dosing guidelines.

According to Dr. Berenson, “Longer infusions are more important than lowering the dose, which is likely to impact its effectiveness.  However, in most patients, this is not necessary; 15 minutes is fine.  However, if the [kidney] function is impaired, it is our practice to slow it down; we do not lower the dose.”

For more information, please see the study in The Journal of Supportive Oncology ^[4] (pdf).