PEGINTRON FOR ADJUVANT MELANOMA

Adjuvant Therapy With Pegylated Interferon Alfa-2b Versus Observation in Resected Stage III Melanoma: A Phase III Randomized Controlled Trial of Health-Related Quality of Life and Symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group

Andrew Bottomley, Corneel Coens, Stefan Suciu, Mario Santinami, Willem Kruit, Alessandro Testori, Jeremy Marsden, Cornelis Punt, François Salès, Martin Gore, Rona MacKie, Zvonko Kusic, Reinhard Dummer, Poulam Patel, Dirk Schadendorf, Alain Spatz, Ulrich Keilholz, Alexander Eggermont

Purpose Interferon (IFN) -based adjuvant therapy in melanoma is associated with significant side effects, which necessitates evaluation of health-related quality of life (HRQOL). Our trial examined the HRQOL effects of adjuvant pegylated IFN--2b (PEG-IFN--2b) versus observation in patients with stage III melanoma.

Methods A total of 1,256 patients with stage III melanoma were randomly assigned after full lymphadenectomy to receive either observation (n = 629) or PEG-IFN--2b (n = 627): induction 6 g/kg/wk for 8 weeks then maintenance 3 g/kg/wk for an intended total duration of 5 years. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 was used to assess HRQOL.

Results At 3.8 years of median follow-up, for the primary end point, recurrence-free survival (RFS), risk was reduced by 18% (hazard rate = 0.82; P = .01) in the PEG-IFN--2b arm compared with observation. Significant and clinically meaningful differences occurred with the PEG-IFN--2b treatment arm compared with the observation group, showing decreased global HRQOL at month 3 (–11.6 points; 99% CI, –8.2 to –15.0) and year 2 (–10.5 points; 99% CI, –6.6 to –14.4). Many of the other scales showed statistically significant differences between scores when comparing the two arms. From a clinical point of view, important differences were found for five scales: two functioning scales (social and role functioning) and three symptom scales (appetite loss, fatigue, and dyspnea), with the PEG-IFN--2b arm being most impaired.

Conclusion PEG-IFN--2b leads to a significant and sustained improvement in RFS. There is an expected negative effect on global HRQOL and selected symptoms when patients undergo PEG-IFN--2b treatment.

Supported by Schering Plough Research International (pegylated interferon alfa-2b provided free of charge).