Tolerability of intensified intravenous interferon alfa-2b versus the ECOG 1684 schedule as adjuvant therapy for stage III melanoma: a randomized phase III Italian Melanoma Inter-group trial (IMI – Mel.A.) [ISRCTN75125874]

摘要: High-dose interferon alfa-2b (IFNalfa-2b), according to the ECOG 1684 schedule, is only approved adjuvant treatment for stage III melanoma patients by FDA and EMEA. However, risk/benefit profile has been questioned limiting its world-wide use. In late nineties, Italian Melanoma Inter-group started a spontaneous randomized clinical trial (RCT) verify if more intense, but shorter than regimen, could improve survival without increasing toxicity profile. The safety analysis in first 169 who completed here described. Stage were receive IFNalfa-2b 20 MU/m2/d intravenously (IV) 5 days/week × 4 weeks, repeated three times on weeks 9 12, 17 20, 25 28 (Dose-Dense/Dose-Intense, DD/DI, arm), or IV followed 10 MU/m2 subcutaneously (SC) per week 48 (High Dose Interferon, HDI, arm). Toxicity was recorded graded, WHO criteria, as worst grade that occurred during each cycle. most common toxicities both arms flu-like gastrointestinal symptoms, leukopenia, liver neuro-psichiatric morbidities; with regard severe toxicity, leukopenia statistically frequent DD/DI arm HDI (24% vs 9%) (p = 0.0074), yet, this did not cause an increase infection risk. Discontinuation of treatment, due observed 13 17% arm, respectively. median actual dose intensity delivered (36.4 MU/m2/week) higher (30.7 0.003). Four cycles intravenous high-dose can be safely intensity. Efficacy results from are eagerly awaited.