Adjuvant high-dose interferon-alpha therapy for high-risk melanoma.

Abstract

The incidence of melanoma continues to rise at a rate greater than all other cancers. Survival in melanoma varies widely by stage, and is affected by a number of prognostic factors including tumour thickness, ulceration and lymph node involvement. New AJCC staging criteria adopted in the 6(th) edition reflect the prognostic value of tumour ulceration, the number of positive lymph nodes as a better prognostic indicator than the size of nodal metastasis, and the similar prognostic value provided by nodal, in-transit and local recurrences. It also recognises the pathologic information about staging provided by lymphatic mapping and sentinel lymphadenectomy. High-risk resected melanoma is defined as disease that after surgery is at higher than 40 to 50% risk of recurrence and death. The urgency to the effort to develop effective therapy for melanoma has led to a wide variety of approaches that have been tested over the years in the high-risk adjuvant setting. Among the many therapeutic modalities tested, the only agent that has shown a significant and reproducible benefit in terms of survival and relapse-free interval has been high-dose interferon-alpha2b. We here review the evidence that has led to the regulatory approval of this regimen, as well as ongoing studies using high-dose interferon-alpha in the high-risk adjuvant setting. We also present selected ongoing trials testing potential future therapies that may prove effective for patients with high-risk resected melanoma.