Melanoma Molecular Maps Projects



Title: Interferon (IFN) alpha for adjuvant treatment of melanoma: a systematic database
Legend: Interferon (IFN) alpha is the only approved treatment in the adjuvant setting for high risk melanoma patients. However, considering the 15 randomized controlled trials (RCT) that have so far tested the efficacy of IFN alpha versus any comparator in TNM stage II-III melanoma patients, the results are not univocal. Consequently, the available findings are fostering a continuous debate on this issue [1-4], also because these RCT have tested different schedules (high or low dose IFN alpha) and have been designed so to compare IFN alpha to different control regimens. Based on the impact of high dose IFN alpha (HDI) on both relapse free survival (RFS, as reported in most RCT and in all meta-analyses) and overall survival (OS, as reported in four RCT [5-8]) some investigators consider this regimen the standard therapy for high risk melanoma patients [9,10]. On the other hand, since the OS benefit is absent in most RCT and in two out of three meta-analyses, some other investigators believe that IFN should not be considered as the adjuvant treatment of choice [11-13]. Recently, an individual patient data (IPD) meta-analysis (considering 85% of patients enrolled in 10 RCT) has shown a significant 3% (CI: 1-5%) absolute reduction in risk of mortality at 5 years (and no difference in RFS was found according to dose or duration of IFN alpha treatment) [14]: considering that the absolute benefit at 5 years of well established adjuvant therapies (i.e. for breast, colorectal, lung and ovarian cancer) ranges between 3% and 9%, the findings of this meta-analysis support the use of IFN alpha. The present Biomap is a systematic collection of RCT of IFN alpha versus any comparator, and includes the three meta-analyses so far performed, the pooled analysis of ECOG 1684 and ECOG 1690 trials, as well as the ongoing RCT addressing the issue of IFN alpha efficacy in the adjuvant treatment of melanoma. REFERENCES: [1] Eggermont AM et al, Surg Oncol Clin N Am 2008, 17:635-48. [2] Garbe C et al, Melanoma Res 2007, 17:117-27. [3] Shah GD et al, Cancer J 2007, 13:217-22. [4] Verma S et al, Cancer 2006, 106:1431-42. [5] Kirkwood JM et al, J Clin Oncol 1996, 14:7-17. [6] Kirkwood JM et al, J Clin Oncol 2000, 18:2444-58. [7] Grob JJ et a, Lancet 1998, 351:1905-10. [8] Garbe C et al, Ann Oncol 2008, 19:1195-201. [9] Moschos SJ et al, J Clin Oncol 2004, 22:11-4. [10] Sondak VK, Lancet 2008, 372:89-90. [11] Lens M, Dermatol Ther 2006, 19:9-18. [12] Bajetta E, Nat Clin Pract Oncol 2008, 5:4-5. [13] Thirlwell C et al, BMJ 2008, 337:a2488. [14] Wheatley K et al, Proc Am Soc Clin Oncol 2007, 25:478S (Abstract 8526).
Author: Sandro Pasquali, MD (University of Padova, Italy) (Update: February 2009)

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