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No Survival Difference Seen In Multiple Myeloma Patients With High-Dose Compared With Low-Dose Thalidomide: Presented at ASCO

By Cameron Johnston

ATLANTA, G.A. -- June 5, 2006 -- Patients with refractory-relapsed multiple myeloma may have equally successful treatment outcomes regardless of whether they receive thalidomide at 100 mg/day or 400 mg/day, researchers reported here at the American Society of Clinical Oncology 2006 Annual Meeting (ASCO).

The findings could be good news for patients who would be spared the added toxicity of the higher dose, without the concern that their survival may be affected.

According to Ibrahim Yakoub-Ahga, MD, hematologist, department of oncology and hematology, University of Lille, Lille, France, thalidomide therapy is rapidly becoming the standard of care for multiple myeloma patients.

However, in a study he conducted in 2002, patients who received 400 mg/day of thalidomide showed an unacceptably high rate of toxicities, but no other dose was tested, he said during a presentation on June 4^th. Such toxicities could be related to the dose used or to the cumulative amount of the drug a patient receives over a given period of time, he said.

To identify the optimal dose of thalidomide, Dr. Yakoub-Ahga and colleagues conducted a noninferiority study that was designed to evaluate the 2 different doses of the drug. They recruited 200 patients with multiple myeloma, and randomized 195 to thalidomide 400 mg/day and 205 to 100 mg/day. Patients were more or less matched for baseline characteristics.

The primary endpoint was overall survival. All patients at enrollment were treated with a bisphosphonate to ensure that the skeleton did not become compromised either as a result of the disease itself or because of the therapy.

No increases in the dosing were permitted, but reductions were allowed. Also, if patients showed an inadequate response or treatment failure within 90 days, they were allowed to receive 40-mg dexamethasone, 4 times per month.

At the end of 1 year of follow-up, there was no significant difference in overall survival between treatment arms: 73% with the 400 mg/day versus 60% with 100 mg/day.

There were significant differences in adverse events; patients receiving the higher dose experienced significantly more somnolence (33% vs 13%), more constipation (40% vs 28%), and more peripheral neuropathy (32% vs 20%) compared with the lower dose, respectively.

No differences were seen in the incidence of deep vein thrombosis, but this could have been due to the trial design, Dr. Yakoub-Ahga said, noting that many patents were receiving anticoagulant therapy, which would have influenced this effect.

These findings suggest that there is "undoubtedly" a dose effect with thalidomide, Dr. Yakoub-Ahga said during a press briefing. He added, however, that there was no difference in overall survival at 1 year between dosing groups.

He recommended that additional trials be conducted in which patients would be treated with dexamethasone from the start, rather than being initiated to steroid therapy once the trial is underway.


[Presentation title: A Multicenter Prospective Randomized Study Testing Non-Inferiority of Thalidomide 100 mg/Day as Compared With 400 Mg/Day in Patients With Refractory-Relapsed Multiple Myeloma: Results of the Final Analysis of IFM 01-02. Poster 7520]

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