Researchers affiliated with the European Organization for Research and Treatment of Cancer (EORTC) have reported that adjuvant pegylated interferon alfa-2b increases recurrence-free survival in patients with Stage III melanoma. The details of this report appeared in the July 12, 2008 issue of The Lancet.¹

Patients with Stage III melanoma have a high rate of distant metastases following surgery alone. Interferon alfa-2b is the only agent currently approved by the U.S. Food and Drug Administration for use as adjuvant therapy in patients with high-risk melanoma following surgical treatment.

Clinical studies evaluating adjuvant interferon following surgery generally show that interferon therapy decreases cancer recurrences and improves survival compared with surgery alone. However, there is still considerable debate over the degree of utility of adjuvant interferon alfa administered in tolerable doses.

Current data may support the use of high-dose interferon for adjuvant therapy, but this can be very toxic and is associated with poor compliance. There is no data to support low-dose interferon adjuvant therapy. Thus, there is also considerable uncertainty about the optimal dose and duration of adjuvant interferon therapy in Stage III melanoma.

A previous study performed by the EORTC evaluated what is called intermediate-dose interferon (see first item of related news). These authors concluded that the adjuvant use of intermediate doses of interferon alfa over one or two years for treatment of Stage IIb/III melanoma had no effect on distant metastasis-free interval or overall survival. They also concluded that patients treated for two years had a slightly better distant metastasis-free interval and overall survival rates than those receiving no treatment; this difference, however, was not deemed statistically significant. They also reported that patients with less disease appeared to benefit more from interferon than those with more extensive disease.

The current study grew out of the above observations. In this study 1,256 patients with Stage III melanoma were randomly allocated to receive pegylated interferon alfa-2b or observation for five years. The median length of treatment with interferon was 12 months, and 31% discontinued treatment due to toxicity. The median follow-up of this study was 3.8 years. The following table summarizes the main findings of this trial:

Pegylated Interferon Alfa-2b Versus Observation in Stage III Melanoma

These authors stated that the effects of interferon were more pronounced in patients with the least amount of disease and in patients with ulcerated disease. These authors suggest that more information is needed to identify patients who are likely to respond to interferon. Patients unlikely to respond need to be spared the toxicities of adjuvant therapy.

Comments: These data help clarify the marginal benefit of adjuvant interferon alfa therapy for Stage III melanoma. However, the benefit of interferon appears to be in prolonging time to relapse, with little impact on ultimate survival.

Related News:

Adjuvant Interferon Alfa May Not Improve Survival in Patients with Stage IIb-III Melanoma. (9/30/2005)

Reference:

¹ Eggermont AMMM, Suciu S, santinami M, et al. Adjuvnt therapy with pegylated interfereon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. The Lancet. 2008;372:117-126.