A randomised phase II trial of 1 month versus 1 year of adjuvant high-dose interferon α-2b in high-risk acral melanoma patients

Abstract

BackgroundHigh-dose Interferon-α-2b (HD-IFN) is an adjuvant treatment for melanoma. However, clinical trials for HD-IFN have not been reported in acral melanoma (AM), the predominant subtype of cutaneous melanoma in Asian population. MethodsPatients with resected high-risk (stage IIb–IIIc) AM were randomly assigned to a regimen of 4-week (arm A: 15×106U/m2d1–5/w×4w) or 1-year adjuvant HD-IFN (arm B: 15×106U/m2d1–5/w×4w+9×106Utiw×48w), respectively. The endpoints were relapse-free survival (RFS), overall survival (OS) and toxicities. ResultsA total of 158 patients were enrolled in this study and 147 patients were eligible for survival analysis. With a median follow-up of 36.1months, median RFS for arm A and arm B were 17.9months and 22.5months, respectively (P=0.72). Stratified analysis showed that RFS curves of patients in stage IIIb–IIIc were statistically different between arm A and arm B (P=0.02). The median RFS of patients with more nodal metastases (n⩾3) was shorter (P=0.004) in arm A (3.3months) than that in arm B (11.9months). Grade 1/2 adverse effects were observed in both groups. However, patients in arm B showed higher incidence of reversible Grade 3/4 hepatotoxicity (P=0.03). ConclusionsThe induction dose of 15×106U/m2 and the maintenance dose of 9×106U were tolerable, which may be the optional dose intensity for adjuvant IFN-α-2b therapy in Chinese high risk AM population. No statistical significance was detected in RFS between the 4-week and 1-year regimen while a 1-year regimen may show clinical benefits in patients with stage IIIb–IIIc AM or with ⩾3 nodal metastases.