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 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 1995 American Society of Hematology meeting in Seattle,Washington, researchers from UCLA School of Medicine presentedresults from a 21-month, phase III clinical study showing thatlong-term pamidronate disodium (Aredia) therapy reduces skeletal-relatedepisodes in patients with stage III multiple myeloma and alsoimproves survival in those on salvage therapy. Pamidronate disodiumis the first medical therapy proven to reduce pathologic fracturesand 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-controlledstudy in which 392 patients were randomized to receive 21 monthsof treatment with 90 mg/month of pamidronate or placebo. Of 392patients, there were 377 evaluable patients (198 given pamidronateand 179, placebo).
21-Month Clinical Results
Patients were stratified by antimyeloma chemotherapy at trialentry (stratum 1: first-line therapy; stratum 2: second-line therapyor higher). After 21 cycles, the proportion of patients experiencingany skeletal event remained smaller in the pamidronate-treatedpatients than the placebo-treated patients (P = .015).In addition, the mean skeletal morbidity rate (number of skeletal-relatedevents per year) was 2.2 in the placebo group vs in the pamidronategroup (P = .008).
Survival of all patients did not differ between the two treatmentgroups. However, after adjustment for the only prognostic factorsfound to be significant for survival in this trial (serum beta-2-microglobulinand 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 welltolerated therapy for the treatment of osteolytic bone lesionsof multiple myeloma," noted Dr. Berenson. "Multiplemyeloma osteolytic bone lesions severely damage the bones, whichmay lead to extreme pain, fractures and spinal cord compression.Until now, we have had to rely on radiation, chemotherapy, surgeryand narcotics to treat the skeletal complications of this disease.This therapy is good news for both the physicians and the patientswho are struggling with the skeletal complications of this deadlycancer."
New Data Support Study's Earlier Results
Dr. Berenson's 21-month data further support evidence he presentedat ASH last year regarding the first part of this study, a 9-monthmulticenter, double-blind, placebo-controlled phase III clinicaltrial in which 377 evaluable patients were randomized to receiveeither 90 mg/mo of pamidronate or placebo in addition to theirantimyeloma 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-treatedpatients suffered any pathologic fractures (P = .004) orneeded any radiation to bone (P = .049). In addition, inthe 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 endpoints of pain, quality of life, and performance status may beoverestimated, 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 andelectrolytes must be monitored closely, as must patients withpreexisting anemia, leukopenia, thrombocytopenia. Pamidronateshould not be used to treat patients with clinically significanthypersensitivity to the drug or other bisphosphonates.
Pamidronate Approved for Treatment of Osteolytic Bone Lesionsof Multiple Myeloma
Pamidronate was first marketed in 1991. The results of this 9-monthstudy led the FDA to clear the drug for marketing in September1995 for the treatment of patients with osteolytic bone lesionsof multiple myeloma in conjunction with standard antimyeloma chemotherapy.Pamidronate is believed to work by inhibiting bone resorptionwithout inhibiting bone formation and mineralization.
Multiple myeloma is a cancer characterized by the proliferationof malignant plasma cells in the bone marrow which, in more thantwo-thirds of patients, results in skeletal complications, suchas fractures due to progressive irreversible bone destruction.In the United States, there are an estimated 50,000 people livingwith multiple myeloma and approximately 13,000 newly diagnosedcases each year. The American Cancer Society estimates that multiplemyeloma will result in approximately 10,000 deaths in 1995. Inaddition to pamidronate, multiple myeloma traditionally has hasbeen treated with chemotherapy,radiotherapy,narcotics, and surgery.