NEW YORK—In phase I trials, AMGN-0007, a new compound to prevent bone metastasis, decreased bone resorption markers to the same extent as the bisphosphonate pamidronate(Drug information on pamidronate) (Aredia), Allan Lipton, MD, professor of medicine, Milton S. Hershey Medical Center, Pennsylvania State University, reported at the Chemotherapy Foundation Symposium XX.
AMGN-0007, or osteoprotegerin, inhibits the osteoprotegerin ligand, the protein that directly activates osteoclasts to resorb bone, Dr. Lipton said. The phase I trial of AMGN-0007 enrolled 54 patients, 26 with breast cancer and 28 with multiple myeloma. All had radiologically identified lytic bone lesions. Estimated extent of skeletal involvement was 10% to 20%. Duration of disease was 5 to 10 years for the breast cancer patients and 3 to 6 years for those with multiple myeloma.
In this double-blind, double-dummy randomized trial, patients who received subcutaneous (SC) doses of AMGN-0007 also were given placebo IV. Those receiving IV pamidronate also got a placebo SC. Patients were given either a single dose of AMGN-0007 at 0.1, 0.3, 1, or 3 mg or a single 90-mg pamidronate dose.
In both the breast cancer and multiple myeloma patients, levels of NTx peptide (cross-linked N-telopeptides of type I collagen(Drug information on collagen)), a marker for bone resorption, fell rapidly in the pamidronate-treated patients and stayed down over the course of the 56-day follow-up.
The lowest dose of AMGN-0007, 0.1 mg/kg, had no apparent effect in either group; 0.3 mg/kg showed some benefit in the multiple myeloma group. The two higher doses of AMGN-0007, 1 mg/kg and 3 mg/kg, led to rapid, sustained decreases in NTx peptide in both the breast cancer and myeloma patients. At these doses, AMGN-0007 dropped the levels of NTx peptide, "as rapidly as did pamidronate but for perhaps a longer period of time," Dr. Lipton said.
Alkaline phosphatase, a marker of bone formation, he added, "usually goes down in patients treated with a bisphos-phonate, shortly after the markers of bone resorption decrease. That’s pretty much what we saw here with pamidronate." Alkaline phosphatase declined with the 1 and 3 mg/kg doses of AMGN-0007 in both breast cancer and myeloma patients. As with pamidronate, the decrease came after the earlier drop in NTx peptide, and was prolonged. The higher AMGN-0007 doses also decreased serum calcium levels, similar to pamidronate, to achieve asymptomatic hypocalcemia.
The results, he said, suggest that a single dose of AMGN-0007 at 1 or 3 mg/kg leads to a rapid, profound, and sustained decrease in bone resorption.
