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 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
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.