High-Potency Bisphosphonate Is Effective for Bone Mets

SAN ANTONIO—Zoledronic acid (Zometa), a high-potency bisphospho-nate, is at least as effective as pamidronate (Aredia) in treating bone metastases, James R. Berenson, MD, said at the 23^rd Annual San Antonio Breast Cancer Symposium. Delivered in a 5-minute infusion, zoledronic acid is expected to be more convenient and easier to use than the older bisphosphonate, said Dr. Berenson, director, Multiple Myeloma and Bone Metastasis Programs, Cedars-Sinai Medical Center, Los Angeles.

In an in vivo system (rat hypercalcemia), zoledronic acid proved more potent than other third-generation bisphos-phonates. Other studies have suggested that the drug may have direct antitumor and antiangiogenesis potential.

The current trial was a randomized, double-blind, dose-response study of 280 patients with multiple myeloma or metastatic breast cancer. The mean time from diagnosis was approximately 16 months, 85% of the patients had reported bone pain to their physicians, 80% had had a skeletal-related event, and half had received prior antineoplastic therapy.

Patients were randomized to receive either pamidronate (90 mg in a 2-hour infusion every 3 to 4 weeks) or zoledro-nic acid in one of three doses (0.4, 2.0, or 4.0 mg in a 5-minute infusion every 3 to 4 weeks). The primary endpoint was the need for radiation therapy to the bone. Treatment continued for 10 months.

Similar Toxicity

Toxicity was similar in the four treatment groups. Adverse events included the expected acute-phase reactions (slight increase in bone pain shortly after injection, low-grade fever, and readily controlled arthralgia and myalgia).

Adding zoledronic acid to the patients’ ongoing therapy did not affect any of the common chemotherapy toxicities. More important, none of the treatments was associated with changes in electrolytes or with renal or mineral disturbances.

"Pain scores decreased slightly in the pamidronate group," Dr. Berenson reported. "And there was a dose-response in the Zometa arm—0.4 mg was less effective than 2.0, and 2.0 was less effective than 4.0 in controlling pain."

Zoledronic acid 0.4 mg was less effective than pamidronate in preventing skeletal-related events (fractures, spinal cord compression, surgery or radiation therapy to the bone, or hypercalcemia of malignancy), but the two higher doses were at least as effective as pamidronate.

At least one skeletal event occurred in 35%, 33%, and 30% of the zoledronic acid 2.0 mg, zoledronic acid 4.0 mg, and pamidronate groups, respectively, he said. In contrast, 46% of the patients in the zoledronic acid 0.4 mg group experienced an adverse skeletal event. The median time to the first event was 167, 175, 231, and 254 days for zoledronic acid 0.4, 2.0, and 4.0, and pamidronate, respectively.

The proportion of patients requiring radiation therapy to the bone was 18% for the pamidronate group and 24%, 19%, and 21% for patients receiving zoledronic acid at 0.4, 2.0, and 4.0 mg, respectively. None of the patients receiving 4.0 mg of zoledronic acid developed hypercalcemia of malignancy.

"In conclusion, Zometa was well tolerated, and no renal toxicity was seen in this study," Dr. Berenson said. "A 5-minute infusion of 4.0 mg of Zometa appears to be at least as effective as 90 mg of pamidronate given as a 2-hour infusion. A dose response was seen in this study, in which the 0.4-mg dose of Zometa was ineffective."