Results of a  recent French study demonstrate that a lower dose of thalidomide may be as effective at treating advanced multiple myeloma as a higher dose, with the benefit of fewer side effects.

Due to the reduced side effects observed with lowered thalidomide dosages, researchers conclude that such a regimen may help to improve quality of life in these patients.

Dr. Ibrahim Yakoub-Agha from the University Hospital in Lille, France, and lead author of the study explained to The Beacon that “Given that higher doses of thalidomide are associated with increased toxicity and are therefore unlikely to be sustained, initiating treatment with 100 mg per day of thalidomide plus dexamethasone should be considered. “

Thalidomide (Thalomid) is widely used to treat both newly diagnosed and relapsed/refractory multiple myeloma patients.  According to Dr. Yakoub-Agha, “Although the anti-myeloma efficacy of thalidomide has been largely established, the side effects of thalidomide are still a matter of concern and may offset the drug’s overall efficacy.”

In the past, researchers have studied thalidomide doses ranging from 50 mg to 1,200 mg per day.  However the optimum dosage has not been determined.

In order to compare the efficacy and safety of low-dose thalidomide to high-dose thalidomide, French researchers analyzed data from a multi-center, randomized trial conducted from 2001 to 2004.  The trial involved 400 patients with relapsed/refractory multiple myeloma.

Nearly half of the patients (42 percent) were older than 70 years, and almost half (46 percent) had received more than two prior lines of therapy.

Patients in the trial were randomly assigned into one of two treatment groups: one group received 100 mg of thalidomide daily, and the other received 400 mg of thalidomide daily.  If, after 12 weeks of thalidomide therapy, patients experienced disease progression or stable disease, dexamethasone (Decadron) was added to the treatment regimen for both groups.

During the first 12 weeks of treatment with thalidomide alone, more patients in the 400 mg treatment group responded to treatment than in the 100 mg treatment group (60 percent compared to 40 percent, respectively).

However, among patients who required the addition of dexamethasone to their treatment, the response rate was similar among the two treatment groups (49 percent for the 400 mg patients, and 45 percent for the 100 mg patients).

Among patients who were able to complete the clinical trial, the one-year overall survival was 75 percent for patients receiving thalidomide at a dose of 400 mg per day and 67 percent for those receiving 100 mg per day.

Patients receiving 100 mg daily experienced significantly fewer thalidomide-related side effects than patients receiving 400 mg daily. The most common side effects were constipation (68 percent in the 100 mg daily dosing group versus 81 percent in the 400 mg daily dosing group), drowsiness (59 percent versus 71 percent), and peripheral neuropathy (56 percent versus 68 percent), a condition characterized by pain and tingling sensations in the extremities.

Among patients receiving 400 mg thalidomide daily, 42 percent required dose reductions due to peripheral neuropathy and other nervous system-related side effects.  In contrast, only 8 percent of patients receiving 100 mg daily required side-effect related dose reductions.

At 48 weeks, more patients in the 100 mg daily dosing group (62 percent) were still receiving their initial dose than in the 400 mg daily dosing group (27 percent).

For more information, please see the European Journal of Haematology (abstract).