Quality of Life in Patients Receiving High-Dose Interferon Alfa-2b After Resected High-Risk Melanoma

Abstract

TO THE EDITOR: We noticed with interest a recent report in Journal of Clinical Oncology on a modified high-dose treatment schedule involving interferon alfa-2b (IFN-2b) for high-risk melanoma. In the standard high-dose IFNregimen registered for adjuvant treatment in high-risk malignant melanoma, 20 10 U/m of IFNis administered intravenously five times per week for 1 month, followed by 48 weeks of 3 10 U/m of IFNsubcutaneously per week. The modified high-dose IFN-2b trial reported by Pectasides et al compared 1 month of high-dose IFN-2b intravenously with 1 month of high-dose IFN-2b intravenously followed by 48 weeks of maintenance therapy with 15 10 U/m of IFN-2b subcutaneously three times per week in the adjuvant treatment of patients with high-risk melanoma. Pectasides et al conclude that no additional benefit of maintenance therapy was detected in overall or relapse-free survival, although the limited sample size allowed for a nearly 10% difference in relapse rates at 3 years. Therefore, the results of additional studies are awaited to clarify the relevance of short-term treatment with highdose IFN-2b in malignant melanoma. A crucial aspect not addressed by the study relates to the quality of life (QoL) of patients during long-term treatment with high-dose IFN-2b. Pectasides et al report on toxicity rates in the 1-year schedule, with a significant difference in neuropsychiatric adverse effects in favor of the 1-month schedule, but there are only single instances of severe toxicity. There is no indication of how patients’ health-related QoL was affected in either treatment arm. In particular, chronic fatigue syndrome could have had a major impact in a significant number of patients, as evidenced by other studies, but this is not reported by Pectasides et al. The MM-ADJ-5 trial by the German Dermatologic Cooperative Oncology Group compared 1 month of high-dose IFN-2b intravenously, repeated three times in 1 year (a pulsed regimen), with standard high-dose IFNin high-risk melanoma patients. An interim analysis of QoL data evaluating the EORTC (European Organisation for Research and Treatment of Cancer) QLQ-C30 questionnaire modified for IFN adverse effects was presented at the 2007 ASCO Annual Meeting, indicating that depression seems to have an unexpectedly low impact on high-dose IFN-2b tolerability, which is in accordance with a recently published observation. In contrast, chronic fatigue syndrome was the most important factor impairing QoL in patients treated with high-dose IFN-2b, and this corresponds to a statistically significant difference in early termination rates in the study by the German Dermatologic Cooperative Oncology Group. Therefore, any comparison between conventional and short-term high-dose IFN-2b treatment should take into account impairment of patients’ QoL, particularly the occurrence of chronic fatigue syndrome.