Temozolomide Plus Interferon Alpha-2b Helpful in Melanoma

Laurie Barclay, MD

July 29, 2004

July 29, 2004 — The combination of temozolomide and interferon-α2b (IFN-α2b) is tolerable and may show a survival advantage in stage IV metastatic melanoma, according to the results of a randomized trial published in the July issue of the British Journal of Dermatology.

"In stage IV disease...median survival is very poor, despite various treatment options, ranging from 3.6 to 11.8 months," write Erika Richtig, MD, from the University of Graz in Austria, and colleagues. "It remains a matter of debate whether the combination of several cytotoxic agents may increase response rate or survival, but combined chemotherapy is defintely more toxic."


In this multicenter, open-label study, 29 male and 18 female patients with stage IV metastatic melanoma were centrally randomized to one of two groups. Twenty patients received temozolomide 150 mg/m2 on days 1 to 5 orally every 28 days, in combination with IFN-α2b 10 MIU/m2 every other day (group A), and 27 patients received temozolomide 150 mg/m2 on days 1 to 5 orally every 28 days, in combination with IFN-α2b in a fixed dose of 10 MIU every other day (group B). Mean age was 57.6 years (range, 34-74 years).

Overall response rate was 27.6%. Complete remission occurred in five patients (10.6%), including one patient in group A and four patients in group B, and persisted through the last follow-up in two of these five patients (4.3%, both in group B). Partial remission occurred in eight patients (17%), including six patients in group A and two patients in group B, and persisted through the last follow-up in three of these eight patients (6.4%), including two patients in group A and one patient in group B. Of three patients (6.4%) with stable disease, one patient was in group A and two patients were in group B.

Mean survival was 14.5 months (95% confidence interval [CI], 10.0 - 19.0 months) with no significant differences between treatment groups. Survival correlated with response after three cycles (P < .03). Of 32 patients who completed at least three cycles of therapy, seven patients (three in group A and four in group B) with a partial or complete response had significantly better mean survival (30.6 months; 95% CI, 19.1 - 42.0 months) than did 25 patients who did not respond (13.7 months; 95% CI, 9.2 - 18.3 months). Overall, survival was longest in patients with at least one complete remission (37.1 months; 95% CI, 26.3 - 47.9 months), followed by patients with at least one partial response (17.4 months; 95% CI, 10.9 - 23.9 months).

There were no treatment-related deaths. Major adverse events were nausea, vomiting, headache, leukopenia, thrombopenia, elevation of liver function enzymes, and neurologica symptoms. Five patients discontinued treatment because of adverse events, including neurologic symptoms (two patients), sepsis (one patient), brain hemorrhage (one patient), and exanthema (one patient).

"The combination of temozolomide and IFN-α2b can easily be administered and shows tolerable toxicity," the authors write. "When an objective response occurs after three cycles, it indicates a significant survival advantage."

AESCA and the Association of Austrian Social Security Institutions supported this study.

Br J Dermatol. 2004;151:91-98

Reviewed by Gary D. Vogin, MD



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