NEW YORKIn phase I trials, AMGN-0007, a new compound to prevent bone
metastasis, decreased bone resorption markers to the same extent as the
bisphosphonate 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
In both the breast cancer and multiple myeloma patients, levels of NTx
peptide (cross-linked N-telopeptides of type I 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.