TY - JOUR
T1 - Post-surgery adjuvant therapy with intermediate doses of interferon alfa 2b versus observation in patients with stage IIb/III melanoma (EORTC 18952)
T2 - Randomised controlled trial
AU - Eggermont, Alexander M.M.
AU - Suciu, Stefan
AU - MacKie, Rona
AU - Ruka, Wlodzimierz
AU - Testori, Alessandro
AU - Kruit, Wim
AU - Punt, Cornelis J.A.
AU - Delauney, Michelle
AU - Sales, François
AU - Groenewegen, Gerard
AU - Ruiter, Dirk J.
AU - Jagiello, Izabella
AU - Stoitchkov, Konstantin
AU - Keilholz, Ulrich
AU - Lienard, Danielle
N1 - Funding Information:
We thank St Jude Children's Research Hospital for provision of an SAS macro that allowed for the computation of the cumulative incidences of distant metastases and of death without distant metastases, due to other causes, and the corresponding treatment comparisons (Gray test). We also thank the previous data managers of this study: A Kirkpatrick, C Molabu. The National Cancer Institute funded the study (grant numbers 5U10 CA11488–26 through 5U10 CA11488–35). The contents of this report are solely the responsibility of the authors and do not represent the official views of the National Cancer Institute (Bethesda, MA, USA). Schering-Plough International also provided an educational grant, and interferon alfa 2b free of charge.
PY - 2005/10/1
Y1 - 2005/10/1
N2 - Background: Individuals affected by melanoma with thick primary tumours or regional node involvement have a poor outlook, with only 30-50% alive at 5 years. High-dose and low-dose interferon alfa have been assessed for the treatment of these patients, with the former having considerable toxicity and a consistent effect on disease free survival, but not on overall survival, and the latter no consistent effect on either. Our aim was, therefore, to assess the effect of two regimens of interferon of intermediate dose versus observation alone on distant metastasis-free interval (DMFI) and overall survival in such patients. Methods: We did a randomised controlled trial in 1388 patients who had had a thick primary tumour (thickness ≥4 mm) resected (stage IIb) or regional lymph node metastases dissected (stage III) and had been assigned to 13-months (n=553) or 25 months (n=556) of treatment with subcutaneous interferon alfa 2b, or observation (n=279). Treatment comprised 4 weeks of 10 million units (MU) of interferon alfa (5 days per week) followed by either 10 MU three times a week for 1 year or 5 MU three times a week for 2 years, to a total dose of 1760 MU. Our primary endpoint was DMFI. Analyses were by intent to treat. Findings: After a median follow-up of 4.65 years, we had recorded 760 distant metastases and 681 deaths. At 4.5 years, the 25-month interferon group showed a 7.2% increase in rate of DMFI (hazard ratio 0.83, 97.5% CI 0.66-1.03) and a 5.4% improvement in overall survival. The 13-month interferon group showed a 3.2% increase in rate of DMFI at 4.5 years (0.93, 0.75-1.16) and no extension of overall survival. Toxicity was acceptable, with 18% (195 of 1076) of patients going off study because of toxicity or as a result of refusal of treatment because of side-effects. Interpretation: Interferon alfa as used in the regimens studied does not improve outcome for patients with stage IIb/III melanomas, and cannot be recommended. With respect to efficacy of the drug, duration of treatment seemed more important than dose, and should be assessed in future trials.
AB - Background: Individuals affected by melanoma with thick primary tumours or regional node involvement have a poor outlook, with only 30-50% alive at 5 years. High-dose and low-dose interferon alfa have been assessed for the treatment of these patients, with the former having considerable toxicity and a consistent effect on disease free survival, but not on overall survival, and the latter no consistent effect on either. Our aim was, therefore, to assess the effect of two regimens of interferon of intermediate dose versus observation alone on distant metastasis-free interval (DMFI) and overall survival in such patients. Methods: We did a randomised controlled trial in 1388 patients who had had a thick primary tumour (thickness ≥4 mm) resected (stage IIb) or regional lymph node metastases dissected (stage III) and had been assigned to 13-months (n=553) or 25 months (n=556) of treatment with subcutaneous interferon alfa 2b, or observation (n=279). Treatment comprised 4 weeks of 10 million units (MU) of interferon alfa (5 days per week) followed by either 10 MU three times a week for 1 year or 5 MU three times a week for 2 years, to a total dose of 1760 MU. Our primary endpoint was DMFI. Analyses were by intent to treat. Findings: After a median follow-up of 4.65 years, we had recorded 760 distant metastases and 681 deaths. At 4.5 years, the 25-month interferon group showed a 7.2% increase in rate of DMFI (hazard ratio 0.83, 97.5% CI 0.66-1.03) and a 5.4% improvement in overall survival. The 13-month interferon group showed a 3.2% increase in rate of DMFI at 4.5 years (0.93, 0.75-1.16) and no extension of overall survival. Toxicity was acceptable, with 18% (195 of 1076) of patients going off study because of toxicity or as a result of refusal of treatment because of side-effects. Interpretation: Interferon alfa as used in the regimens studied does not improve outcome for patients with stage IIb/III melanomas, and cannot be recommended. With respect to efficacy of the drug, duration of treatment seemed more important than dose, and should be assessed in future trials.
UR - http://www.scopus.com/inward/record.url?scp=25844465690&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(05)67482-X
DO - 10.1016/S0140-6736(05)67482-X
M3 - Article
C2 - 16198768
AN - SCOPUS:25844465690
SN - 0140-6736
VL - 366
SP - 1189
EP - 1196
JO - Lancet
JF - Lancet
IS - 9492
ER -