“We found that using prednisone following a response to up-front chemotherapy was an effective and safe way to prolong the lives of patients,” said James Berenson, M.D., lead author of the Southwest Oncology Group sponsored study and Director of the Multiple Myeloma and Bone Metastasis Program at Cedars-Sinai Medical Center. “This is the first clear demonstration that long term treatment following an initial response to chemotherapy improves the survival of patients with multiple myeloma.”
Multiple myeloma occurs when the body makes an abnormally high number of cancerous plasma cells. When healthy, plasma cells help to protect the body from infection and disease by forming antibodies that attack foreign substances. But when the body makes too many plasma cells that all make the same type of antibody, this leads to multiple myeloma, causing damage to bones, severe bone pain, an overabundance of calcium in the blood, anemia, and a weakening of the immune system. Today, most patients with multiple myeloma receive initial treatment with chemotherapy or with high-dose chemotherapy followed by a stem cell transplant and many respond to treatment and achieve remission. However, all patients ultimately relapse with incurable disease, leading physicians to search for ways to prolong remission for as long as possible by using some type of maintenance therapy.
Although some studies have shown that interferon (an antiviral drug) slightly prolongs remission in patients with multiple myeloma, it has not been shown to improve their overall survival. Steroids, however, have been found to inhibit tumor growth in multiple myeloma. Prednisone, for example, is a steroid that can be taken in pill-form and has been combined with up front chemotherapy to help shrink tumors and bring patients into remission. The drug has also been evaluated in combination with interferon as maintenance therapy, with some studies showing that remission was prolonged. But no prior studies to date have examined whether prednisone alone could prolong remission as well as improve overall survival for patients with multiple myeloma.
“We wanted to find out whether prednisone alone, a drug that was easy to take and had fewer side effects, was effective as maintenance therapy without the toxicities and costs associated with interferon,” said Dr. Berenson.
In the study, the researchers compared patients with multiple myeloma receiving prednisone in pill-form following a response to treatment with one of two chemotherapy combinations: vincristine, doxorubicin and dexamethasone with prednisone or with or without quinine, which has been found to increase the effectiveness of chemotherapy. Treatment with either of the chemotherapy combinations was repeated every 21 days for at least six months, or until patients achieved at least a 25 percent reduction in tumor size. After a 53-month follow-up period, the investigators found that there was no difference in either progression-free or overall survival between the patients receiving chemotherapy with or without quinine.
To determine whether prednisone alone was effective as maintenance therapy, patients who responded to treatment with up-front chemotherapy were randomly selected to receive either 10 (the amount that the body normally makes daily) or 50 mg of prednisone every other day until their disease progressed. From the time that maintenance therapy started, the researchers found that patients receiving the higher dose of prednisone remained free of disease progression for 14 months versus five months for patients receiving the lower dosage. Most importantly, the investigators found that patients receiving the higher doses of prednisone lived significantly longer (37 months versus 26 with the lower dose).
“We found that the long term use of prednisone delayed progression of the disease and kept patients alive longer. Furthermore, 50 mg of prednisone every other day was well tolerated, which means that patients remain active and have a much better quality of life for longer,” said Dr. Berenson.
Future studies will examine whether prednisone is effective to prolong remission for patients with other cancers such as leukemia or lymphoma. In addition, other drug combinations that include prednisone will be evaluated as maintenance therapy for patients with multiple myeloma.
Cedars-Sinai Medical Center is one of the largest and finest non-profit hospitals in the Western United States. For the fifth straight two-year period, Cedars-Sinai has been named Southern California’s gold standard in health care in an independent survey. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthrough biomedical research and superlative medical education. The Medical Center ranks among the top seven non-university hospitals in the nation for its research activities.
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Blood