Thalidomide, a drug often used to treat symptoms of leprosy and in testing to fight HIV, is now demonstrating activity in fighting a common cancer that occurs in bone marrow, myeloma.
According to two studies presented during the 46th Annual Meeting of the American Society of Hematology, thalidomide may play an important role in fighting the disease both during initial treatment and as maintenance therapy. Myeloma is caused by an abnormality in plasma cells, which are the cells that synthesize and secrete antibodies that are crucial in fighting infections. Thus disorders of plasma cells reduce the body's protection against infection.
Researchers need to be cautiously observant of side effects and toxicities that may be associated with thalidomide. However these studies suggest that patients suffering from myeloma may benefit significantly by adding the therapy to their treatment regimens.
Thalidomide Plus Dexamethasone Versus Dexamethasone Alone in Newly Diagnosed Multiple Myeloma (E1A00): Results of a Phase III Trial Coordinated by the Eastern Cooperative Oncology Group
A new study by researchers of the Eastern Cooperative Oncology Group suggests that the addition of thalidomide to a standard treatment regimen for multiple myeloma may be significantly more beneficial to patients suffering from the disease. The standard treatment used was dexamethasone, a chemical equivalent of a steroid-like hormone in the body.
In the trial, patients with newly-diagnosed, untreated, symptomatic disease were randomized and treated in one of two arms: Arm A (103 pts), thalidomide (200 mg/day orally) plus dexamethasone (40 mg) (Thal/Dex); or Arm B (104 pts), dexamethasone alone (40 mg) (Dex). Therapy was repeated monthly, with a primary endpoint of best response at four months on intent to treat basis.
Analyses from 198 of the patients demonstrated a significantly higher response rate with Thal/Dex (58 percent) than with Dex alone (42 percent). Interestingly, the average time to response was rapid and similar in both arms, at approximately one month. Within the first four months, confirmed disease progression occurred in just three percent of patients in the Thal/Dex arm and five percent in the Dex arm.
To note, grade three or greater non-hematologic toxicities occurred within the first four months in 68 percent of patients in the Thal/Dex arm, compared with only 43 percent in the Dex arm. Grade three or higher cardiac ischemia (blockage in the coronary artery) occurred in three patients in Arm A and two patients in Arm B.
"While we feel that this therapy should be carefully considered on an individual basis due to the higher toxicity level, we are confident that the combination does demonstrate a superior response in newly diagnosed multiple myeloma patients," said S. Vincent Rajkumar, M.D., of the Mayo Clinic, Rochester, MN, and lead author on the study. "The regimen offers a better option than standard treatment with intravenous VAD and negates its use in patients suffering from this disease." VAD is a standard combination therapy cycle using vincristine, adriamycin and dexamethasone.
Maintenance Treatment with Thalidomide after Autologous Transplantation for Myeloma: First Analysis of a Prospective Randomized Study of the Intergroupe Francophone du Myelome (IFM 99 02)
To treat aggressive myeloma, hematologists have relied on high dose therapy (HDT) with autologous stem cell transplantation, a process which uses the patient's own healthy stem cells to fight the infection. However, because most patients who undergo this therapy eventually relapse, new strategies are being tested to manage the residual disease after HDT. Results from a new study by researchers at the Hopital Purpan in France suggest that thalidomide may be a new and effective maintenance treatment for this use.
The Intergroupe Francophone du Myelome (IFM) initiated a trial to evaluate the value of thalidomide in this setting, enrolling 780 myeloma patients under the age of 65. The group received standard chemotherapy treatment plus two autologous transplants. Those patients without progressive disease after two months (580 pts, 74 percent) were then randomized to receive: no maintenance treatment (Arm A, 195 pts); maintenance treatment with pamidronate, a standard therapy used to treat bone diseases (Arm B, 190 pts); or maintenance treatment with thalidomide and pamidronate (Arm C, 195 pts).
At 40 months post-diagnosis, the researchers found that thalidomide improved the progression-free survival (PFS) and the event-free survival (EFS) rates. The probability of PFS in the thalidomide arm was 70 percent, compared with 53 percent in Arm A and 52 percent in Arm B. Most patients in the other trial arms received thalidomide when the disease relapsed, and overall survival was similar in the three groups.
"In the results, we acknowledge that two main factors were associated with a longer event-free survival for our patients: treatment arm, and low beta-2- microglobulin [a protein present on the surface of plasma cells and lymphocytes] at diagnosis," said Michel Attal, M.D., of the Hopital Purpan in Toulouse, France and lead author of the study. "We are confident of thalidomide's utility as a maintenance therapy for this patient population and look forward to confirming our results with additional trials."
According to the American Cancer Society, there have been more than 15,000 new cases of multiple myeloma this year in the United States, and about 11,000 Americans will have died of the disease.