An Arkansas Cancer Research Center study,
published in the November 18, 1999, issue of The New England
Journal of Medicine, found that thalidomide (Thalidomid)
effectively reduced or, in some cases, eliminated tumor activity in
multiple myeloma patients who had not responded previously to other agents.
The phase II study of 84 patients with progressive disease found that
10% enjoyed a complete or near-complete remission, and 32%
experienced a reduction in serum or urine paraproteins of at least
25%. To qualify as a response, the reduction in paraproteins must
have been observed minimally twice, at 6-week intervals. In addition,
a majority of patients exhibited other evidence of antitumor
activity, said Bart Barlogie,MD, PhD, director of the Arkansas Cancer
Research Center, and the studys principal investigator. These
included a reduction in the percentage of plasma cells in bone marrow
and an increase in blood hemoglobin levels.
Responses Maintained Over the Follow-up Period
According to Dr. Barlogie, responses were observed in 78% of patients
within 2 months of beginning thalidomide therapy, with nearly all
patients demonstrating a response within 4 months. The study included
76 patients whose disease had previously relapsed following high-dose
chemotherapy. Responses to thalidomide were maintained over the
12-month follow-up period in the majority of patients.
These findings of the activity of thalidomide in multiple
myeloma have been subsequently confirmed by other investigators,
further strengthening the position of thalidomide as a potential
top-line therapy for myeloma patients, said Dr. Barlogie.
In my opinion, these data place thalidomide in a class with
melphalan (Alkeran) and glucocorticoids as the most promising
treatment options for multiple myeloma patients.
Being an advocate for improved solutions for all myeloma
patients and a patient myself, I am very encouraged by the study
results coming out of the Arkansas Cancer Research Center, said
Kathy Giusti, president of the Multiple Myeloma Research Foundation.
To finally have evidence that there may be another weapon
against this awful disease is exciting.
Inhibition of Angiogenesis
Thalidomide may be exerting its activity by inhibition of the
angiogenesis induced by multiple myeloma, said Dr. Barlogie.
Coupled with the fact that thalidomide doesnt appear to
cause an array of adverse effects traditionally associated with
chemotherapy, the study suggests that the drug could be an ideal
agent for use in combination with other chemotherapeutic regimens. We
are currently investigating this hypothesis with a $13.5 million
research grant from the National Institutes of Health. By
understanding how thalidomide works against multiple myeloma, we hope
to better understand myeloma cell behavior and thus develop novel
strategies to combat and ultimately cure this disease.
More than one-third of the studys patients experienced some
adverse effects, including constipation, weakness or fatigue, and
somnolence. Reducing the dose of thalidomide alleviated these adverse
effects in most patients.