intermediate-dose interferon trial, the end had been reached for low-dose interferon in Europe. In the United States, low-dose interferon has never been routinely employed for melanoma. It is noteworthy that low-dose interferon has been licensed in the European Community for intermediate-risk primary melanoma, based on early data suggesting a relapse-free survival advantage for that regimen.

In the United States, a number of large cooperative group studies have compared a regimen of intravenous high-dose induction therapy followed by maintenance high-dose interferon with observation or vaccine therapy for high-risk disease (Table 20.3). The only equivalent trial in Europe is the EORTC 18952 trial, which we discuss later. Three well-powered trials have tested high-dose interferon as adjuvant therapy for resected high-risk melanoma, although the best quality data suggesting an advantage in relapse-free and overall survival are derived from the smallest and oldest trial, the EST 1684 trial of 280 patients.51 In that trial, patients were randomized to either observation or the by now standard high-dose regimen of 20 million units/m2 intravenously daily times five for 4 weeks in the induction phase. The maintenance phase ensued in which interferon was administered at a dose of 10 million units/m2 subcutaneously three times a week for 11 months. In that trial, one-third of the patients either discontinued the regimen or required a dose modification because of toxicity. The differences in relapse-free and overall survival significantly favored the interferon arm, with 5-year survival of 37%, median survival of 2.78 years, and P = 0.04. Interestingly, over time the advantage for overall survival has diminished with P = 0.09 at 12 years follow-up, although other causes of death in that aging cohort may obscure the results. Following the EST 1684 study, the U.S. Intergroup performed two subsequent trials of high-dose interferon. In the EST 1690 trial, 683 patients were randomly allocated to receive either observation, high-dose interferon, or the European regimen of a fixed low interferon dose of 3 million units three times a week for 2 years.52 No differences in overall or even relapse-free survival were seen in that larger trial. As accrual to that trial ended, a follow-up trial comparing high-dose interferon with a ganglioside vaccine for 2 years in high-risk patients was initiated. In that EST 1694 trial, 780 patients were accrued, and the study was stopped prematurely, because there was a significant difference in relapse-free survival favoring the interferon arm with a very low P value of 0.01 that met the monitoring committee requirement for early closure.53 A statistically significant difference in overall survival was also observed in that trial, with a relatively brief period of follow-up. A fourth smaller trial of high-dose interferon, interferon with ganglioside, and ganglioside alone was conducted, with relapse-free survival data similar to the 1694 trial, albeit with small numbers and brief follow-up.54 The conclusion from an analy

How To Prevent Skin Cancer

How To Prevent Skin Cancer

Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.

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