SAN ANTONIOZoledronic 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 23rd 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
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.
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
"Pain scores decreased slightly in the pamidronate
group," Dr. Berenson reported. "And there was a dose-response in the
Zometa arm0.4 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
"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."