Current approaches to adjuvant therapy of melanoma

Abstract

The incidence of malignant melanoma is rising faster than any other solid tumour and in young adults melanoma is the most common tumour type. In spite of improved early recognition and early treatment melanoma mortality rates are increasing. The therapeutic management of melanoma is challenging and the tumour remains among the most resistant tumour types to medical treatment. Surgical removal of the primary tumour is virtually the only curative approach presently available. To prevent disease recurrence in high-risk patients, stage IIB–IIC disease without lymph-node metastases or stage III, who have a 5-year survival of 24−67% [1] different adjuvant treatments have been tested. Up to now interferon alfa-2b has been the most frequently investigated. The Eastern Cooperative Oncology Group (ECOG) E1684 Trial demonstrated prolonged relapsefree survival (RFS) and prolonged overall survival in patients treated with adjuvant high-dose interferon alfa-2b [2]. In the confirmatory Trial E1690, however, this survival benefit could not be reproduced. The E1690 Trial showed improved RFS, but did not show a benefit in overall survival with the high-dose interferon alfa-2b regimen [3]. Since the toxic effects of the high-dose interferon regimen has been of concern the question was raised whether lower doses of interferon alfa-2b would be a less toxic alternative to high doses. The EORTC 18952 Trial explored intermediate-dose interferon alfa-2b and showed significant improvement in RFS, but no effect on overall survival [4]. Similarly, the recent Nordic Melanoma Collaborative Group Trial [5] also demonstrated a significant improvement in RFS compared with untreated controls, but no survival benefit. In the 18991 EORTC Trial with pegylated interferon alfa-2b (PEG-IFN-alfa-2b), a drug preparation allowing more convenient drug administration, i.e. once-weekly injection, demonstrated significant prolongation of RFS, but no significant improvement in overall survival [6]. Meta-analysis