Systematic review suggests possible benefit for high dose interferon in high-risk melanoma

This Canadian review looking at the role of adjuvant treatment in resected high-risk melanoma, found no survival benefit for most adjuvant systemic treatment but high dose interferon appears to improve disease free survival and reduce two-year mortality.The Canadian Melanoma Disease Site Group (DSG) has conducted an overview of published studies on the adjuvant treatment of surgically resected melanoma. The authors discussed the rising incidence of melanoma in Canada and the need for effective adjuvant treatment. They described the promising early results of immunotherapy studies and the controversy surrounding the more mature data.They reviewed the literature from 1980 and 2004 and identified 37 randomised controlled trials, two meta-analyses, and one systematic review which involved the use of interferon, levamisole, vaccines, or chemotherapy. Studies of other agents such as BCG were not included. The relevant end points included overall survival, recurrence-free survival, adverse effects, and quality of life. High-risk criteria included tumor thickness 4.0 mm, Level V invasion, in-transit or regional lymph node metastases or regional lymph node recurrence.No significant survival benefit was seen in the four levamisole, nine vaccine or ten chemotherapy trials. The review concentrated on the role of interferon a and no statistically significant survival advantage was found in five randomised trials comparing low-dose interferon-a with observation after surgery. However, the pooled data from the three ECOG randomized trials of high dose interferon did show a significant reduction in deaths at two years (RR 0.85, 95% CI, 0.73-0.99, p = 0.03). The authors concluded that no systemic adjuvant therapy produced a significant long term overall survival benefit in patients with high-risk, resected, primary melanoma. However, high-dose interferon should be considered as it was associated with a significant improvement in disease-free survival and a reduction in 2-year mortality. It is not yet known whether it also benefits patients with microscopically detected, sentinel lymph node-positive disease. They stressed the need for further studies of new agents and stated that observation could still be considered as the control arm in such studies. The Group has published its guidelines on the internet, at www.cancercare.on.ca/index_melanomaGuidelines.htm.Reference...