Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-13909

Eggermont, A M M; Suciu, S; Santinami, M; Testori, A; Kruit, W H J; Marsden, J; Punt, C J A; Salès, F; Gore, M; Mackie, R; Kusic, Z; Dummer, R; Hauschild, A; Musat, E; Spatz, A; Keilholz, U (2008). Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet, 372(9633):117-126.

[img]
Preview
Accepted Version
PDF
248kB

Abstract

BACKGROUND: Any benefit of adjuvant interferon alfa-2b for melanoma could depend on dose and duration of treatment. Our aim was to determine whether pegylated interferon alfa-2b can facilitate prolonged exposure while maintaining tolerability. METHODS: 1256 patients with resected stage III melanoma were randomly assigned to observation (n=629) or pegylated interferon alfa-2b (n=627) 6 mug/kg per week for 8 weeks (induction) then 3 mug/kg per week (maintenance) for an intended duration of 5 years. Randomisation was stratified for microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumour thickness, sex, and centre. Randomisation was done with a minimisation technique. The primary endpoint was recurrence-free survival. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00006249. FINDINGS: All randomised patients were included in the primary efficacy analysis. 608 patients in the interferon group and 613 patients in the observation group were included in safety analyses. The median length of treatment with pegylated interferon alfa-2b was 12 (IQR 3.8-33.4) months. At 3.8 (3.2-4.2) years median follow-up, 328 recurrence events had occurred in the interferon group compared with 368 in the observation group (hazard ratio 0.82, 95% CI 0.71-0.96; p=0.01); the 4-year rate of recurrence-free survival was 45.6% (SE 2.2) in the interferon group and 38.9% (2.2) in the observation group. There was no difference in overall survival between the groups. Grade 3 adverse events occurred in 246 (40%) patients in the interferon group and 60 (10%) in the observation group; grade 4 adverse events occurred in 32 (5%) patients in the interferon group and 14 (2%) in the observation group. In the interferon group, the most common grade 3 or 4 adverse events were fatigue (97 patients, 16%), hepatotoxicity (66, 11%), and depression (39, 6%). Treatment with pegylated interferon alfa-2b was discontinued because of toxicity in 191 (31%) patients. INTERPRETATION: Adjuvant pegylated interferon alfa-2b for stage III melanoma has a significant, sustained effect on recurrence-free survival.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
DDC:610 Medicine & health
Language:English
Date:2008
Deposited On:18 Feb 2009 09:50
Last Modified:02 Dec 2013 06:09
Publisher:Elsevier
ISSN:0140-6736
Publisher DOI:10.1016/S0140-6736(08)61033-8
PubMed ID:18620949
Citations:Web of Science®. Times Cited: 226
Google Scholar™
Scopus®. Citation Count: 270

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page