ROCKVILLE, Md--In a move with very little precedent, the FDA Oncologic
Drugs Advisory Committee (ODAC) recommended approval of a new
indication for the bisphosphonate Aredia (pam-idronate disodium
for injection) on the basis of a single clinical trial.
The new indication is for the treatment of bone metastases associated
with multiple myeloma. The drug is already approved for use in
hypercalcemia of malignancy (October 1991) and Paget's disease
The committee felt that even though the drug's sponsor, Ciba Pharmaceutical
Division, Ciba-Geigy Corp., presented only one phase III clinical
trial, the need for the drug is so great and the adverse reactions
sufficiently tolerable, that Aredia should be made available to
people with multiple myeloma.
James Berenson, MD, associate professor of medicine, University
of California, Los Angeles, and chief of oncology, Veterans Administration
Medical Center, told the panel that multiple myeloma is the second
most common hematologic malignancy in the United States, with
12,500 new cases each year. Sixty percent of patients are already
at stage III when they are first diagnosed.
Among the many clinical features of multiple myeloma are serious
skeletal complications such as osteoporosis, lytic lesions, pathologic
fractures, osteopenia, and spinal cord compression. Treatment
with analgesics, radiation therapy, surgery, glucocorticosteroids,
and chemotherapy has been less than successful, Dr. Berenson said.
John Seaman, PharmD, director of clinical research, Ciba Pharmaceuticals
Division, described the randomized, double-blind clinical trial
of Aredia vs placebo in which 392 patients with stage III multiple
myeloma participated. All had at least one lytic lesion.
The goal was to compare the effects of Aredia and placebo on spinal
cord compression or collapse, pathologic fracture, and need for
radiation to treat bone and prevent fractures. Pain, narcotic
use, bone lesion response, and quality of life also were evaluated.
In general, all patients were receiving appropriate anticancer
drugs, most commonly melphalan (Alkeran) and prednisone.