ROCHESTER, Minn. -- From the late 1950s to the end of 1961, thalidomide was a popular sedative and treatment for morning sickness until it was discovered to cause fetal malformations, which proved fatal within the first year of life in 40 percent of affected infants.
The drug was never marketed in the United States or approved by the U.S. Food and Drug Administration. But researchers recognized the drug's properties might have cancer-fighting potential. This possibility has driven promising studies into thalidomide's role in fighting blood disorders, such as multiple myeloma, a deadly cancer for which there is no cure. Mayo Clinic Proceedings' July issue offers four studies that have probed thalidomide's promising future after its tragic past.
"The most common indication for thalidomide use today is multiple myeloma and related plasma cell disorders," says S. Vincent Rajkumar, M.D., a hematologist at Mayo Clinic in Rochester, in a commentary article in the July issue of Mayo Clinic Proceedings. "Thalidomide represents a new era in therapy for this incurable and fatal malignancy."
But, says Dr. Rajkumar, one of the top researchers into thalidomide's role in multiple myeloma, "Clinical trials eventually will determine whether thalidomide will be used as an anticancer agent in the long term or will be pushed into retirement by one or more safer analogues."
The July issue of Mayo Clinic Proceedings includes studies and editorials regarding thalidomide and myeloma:
Mayo Clinic researchers present findings in a long-term follow-up of patients with monoclonal gammopathy of undetermined significance (241 patients were examined at Mayo Clinic from 1956 to 1970) and found that the risk of progression to multiple myeloma or related cancer is indefinite and persists even after more than 30 years of follow-up. In an editorial, Joan Bladé, M.D., a hematologist at Hospital Clínic IDIBAPS in Barcelona, Spain, writes that Robert Kyle, M.D., a Mayo Clinic hematologist who led the study, first recognized the possibility of malignant transformation of monoclonal gammopathy. Because of Dr. Kyle's detailed studies, physicians have learned about the actual outcome of persons with monoclonal gammopathy of undetermined significance, Bladé writes.
Mayo Clinic researchers report their findings in patients who've had relapses in multiple myeloma, noting that the response duration of the follow-up treatment or salvage therapy decreased. The researchers said this must be remembered when making treatment decisions for these patients and must be factored in when assessing the efficacy of new therapies.
Researchers from Dana-Farber Cancer Institute in Boston; Celgene Corporation in Warren, N.J.; St. Vincents Catholic Medical Center in New York; and H. Lee Moffitt Cancer Center in Tampa studied the dosage of thalidomide for patients with relapsed multiple myeloma after high-dose chemotherapy and stem cell transplantation. They report that the optimal thalidomide dose varies and should be based on individual patients to ensure that it is well tolerated and a response is achieved.
When thalidomide is used alone or combined with prednisone, it can also be an effective frontline treatment for symptomatic anemia or low platelets in patients with myelofibrosis with myeloid metaplasia, a chronic form of leukemia. The Mayo Clinic College of Medicine researchers outline their findings regarding 36 patients. In an editorial about this study, Richard Silver, M.D., of New York-Presbyterian Hospital-Weill Cornell Medical Center in New York, writes that the results provide an important therapeutic contribution in terms of quality of life.
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A peer-review journal, Mayo Clinic Proceedings publishes original articles and reviews dealing with clinical and laboratory medicine, clinical research, basic science research and clinical epidemiology. Mayo Clinic Proceedings is published monthly by Mayo Foundation for Education and Research as part of its commitment to the medical education of physicians. The journal has been published for more than 75 years and has a circulation of 130,000 nationally and internationally. Copies of the articles will be available online after the embargo lifts at www.mayo.edu/proceedings.
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Mayo Clinic Proceedings
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