At the 1995 American Society of Hematology meeting in Seattle, Washington, researchers from UCLA School of Medicine presented results from a 21-month, phase III clinical study showing that long-term pamidronate(Drug information on pamidronate) disodium (Aredia) therapy reduces skeletal-related episodes in patients with stage III multiple myeloma and also improves survival in those on salvage therapy. Pamidronate disodium is the first medical therapy proven to reduce pathologic fractures and other skeletal complications in patients with multiple myeloma.
At the Seattle meeting, principal investigator James Berenson, MD, Associate Professor of Medicine, UCLA School of Medicine, and Chief of Medical Oncology, DVA Medical Center, West Los Angeles, reviewed results of the large, multicenter, placebo-controlled study in which 392 patients were randomized to receive 21 months of treatment with 90 mg/month of pamidronate or placebo. Of 392 patients, there were 377 evaluable patients (198 given pamidronate and 179, placebo).
21-Month Clinical Results
Patients were stratified by antimyeloma chemotherapy at trial entry (stratum 1: first-line therapy; stratum 2: second-line therapy or higher). After 21 cycles, the proportion of patients experiencing any skeletal event remained smaller in the pamidronate-treated patients than the placebo-treated patients (P = .015). In addition, the mean skeletal morbidity rate (number of skeletal-related events per year) was 2.2 in the placebo group vs in the pamidronate group (P = .008).
Survival of all patients did not differ between the two treatment groups. However, after adjustment for the only prognostic factors found to be significant for survival in this trial (serum beta-2-microglobulin and ECOG performance status), stratum 2 patients (on salvage chemotherapy) receiving pamidronate showed a significant improvement in survival, as compared with similar patients given placebo (median survival, 20.6 vs 14.1 mos; P = .041)
"Our studies show that Aredia is a safe and generally well tolerated therapy for the treatment of osteolytic bone lesions of multiple myeloma," noted Dr. Berenson. "Multiple myeloma osteolytic bone lesions severely damage the bones, which may lead to extreme pain, fractures and spinal cord compression. Until now, we have had to rely on radiation, chemotherapy, surgery and narcotics to treat the skeletal complications of this disease. This therapy is good news for both the physicians and the patients who are struggling with the skeletal complications of this deadly cancer."
New Data Support Study's Earlier Results
Dr. Berenson's 21-month data further support evidence he presented at ASH last year regarding the first part of this study, a 9-month multicenter, double-blind, placebo-controlled phase III clinical trial in which 377 evaluable patients were randomized to receive either 90 mg/mo of pamidronate or placebo in addition to their antimyeloma chemotherapy regimen. In this phase of the study, 41% of patients receiving placebo developed a skeletal complication (fractures, local irradiation, spinal compression, and/or surgery), as compared with 24% of those taking pamidronate. Fewer pamidronate-treated patients suffered any pathologic fractures (P = .004) or needed any radiation to bone (P = .049). In addition, in the pamidronate-treated patients with pain at baseline, pain scores (a secondary variable) decreased at study's end (P = .026). The statistical significance of analyses of these secondary end points of pain, quality of life, and performance status may be overestimated, however, since numerous analyses were performed.
The most common adverse experiences, regardless of drug relationship, were fever, anemia, nausea, upper respiratory tract infection, and fatigue. When pamidronate is prescribed, serum calcium and electrolytes must be monitored closely, as must patients with preexisting anemia, leukopenia, thrombocytopenia. Pamidronate should not be used to treat patients with clinically significant hypersensitivity to the drug or other bisphosphonates.
Pamidronate Approved for Treatment of Osteolytic Bone Lesions of Multiple Myeloma
Pamidronate was first marketed in 1991. The results of this 9-month study led the FDA to clear the drug for marketing in September 1995 for the treatment of patients with osteolytic bone lesions of multiple myeloma in conjunction with standard antimyeloma chemotherapy. Pamidronate is believed to work by inhibiting bone resorption without inhibiting bone formation and mineralization.
Multiple myeloma is a cancer characterized by the proliferation of malignant plasma cells in the bone marrow which, in more than two-thirds of patients, results in skeletal complications, such as fractures due to progressive irreversible bone destruction. In the United States, there are an estimated 50,000 people living with multiple myeloma and approximately 13,000 newly diagnosed cases each year. The American Cancer Society estimates that multiple myeloma will result in approximately 10,000 deaths in 1995. In addition to pamidronate, multiple myeloma traditionally has has been treated with chemotherapy,radiotherapy,narcotics, and surgery.