Adjuvant therapy with pegylated interferon alfa-2b versus observation in resected stage III melanoma: a phase III randomized controlled trial of health-related quality of life and symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group.
OBJECTIVE
Interferon (IFN) -based adjuvant therapy in melanoma is associated with significant side effects, which necessitates evaluation of health-related quality of life (HRQOL). Our trial examined the HRQOL effects of adjuvant pegylated IFN-alpha-2b (PEG-IFN-alpha-2b) versus observation in patients with stage III melanoma.


METHODS
A total of 1,256 patients with stage III melanoma were randomly assigned after full lymphadenectomy to receive either observation (n = 629) or PEG-IFN-alpha-2b (n = 627): induction 6 micrograms/kg/wk [DOSAGE ERROR CORRECTED] for 8 weeks then maintenance 3 micrograms/kg/wk [DOSAGE ERROR CORRECTED] for an intended total duration of 5 years. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 was used to assess HRQOL.


RESULTS
At 3.8 years of median follow-up, for the primary end point, recurrence-free survival (RFS), risk was reduced by 18% (hazard rate = 0.82; P = .01) in the PEG-IFN-alpha-2b arm compared with observation. Significant and clinically meaningful differences occurred with the PEG-IFN-alpha-2b treatment arm compared with the observation group, showing decreased global HRQOL at month 3 (-11.6 points; 99% CI, -8.2 to -15.0) and year 2 (-10.5 points; 99% CI, -6.6 to -14.4). Many of the other scales showed statistically significant differences between scores when comparing the two arms. From a clinical point of view, important differences were found for five scales: two functioning scales (social and role functioning) and three symptom scales (appetite loss, fatigue, and dyspnea), with the PEG-IFN-alpha-2b arm being most impaired.


CONCLUSIONS
PEG-IFN-alpha-2b leads to a significant and sustained improvement in RFS. There is an expected negative effect on global HRQOL and selected symptoms when patients undergo PEG-IFN-alpha-2b treatment.
Bottomley
Andrew
A
Quality of Life Department, EORTC Headquarters, Brussels, Belgium. andrew.bottomley@eortc.be
Coens
Corneel
C
Suciu
Stefan
S
Santinami
Mario
M
Kruit
Willem
W
Testori
Alessandro
A
Marsden
Jeremy
J
Punt
Cornelis
C
Salès
François
F
Gore
Martin
M
Mackie
Rona
R
Kusic
Zvonko
Z
Dummer
Reinhard
R
Patel
Poulam
P
Schadendorf
Dirk
D
Spatz
Alain
A
Keilholz
Ulrich
U
Eggermont
Alexander
A
D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols; D011788:Quality of Life; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b