Randomized phase III study of 1 month versus 1 year of adjuvant high-dose interferon alfa-2b in patients with resected high-risk melanoma.
OBJECTIVE
A high-dose interferon alfa (IFN-alpha) regimen as reported in E1684 was unique for the incorporation of an induction phase of maximally tolerated dosages of intravenous (IV) therapy for the initial 4 weeks. This is the only trial that has shown prolongation of overall survival and relapse-free survival (RFS) in comparison with observation. Analysis of the hazard curves for RFS and overall survival (OS) in E1684 revealed separation of the high-dose and observation arms, suggesting that the induction phase may represent a critical component of this regimen, although this has not been tested prospectively.


METHODS
We conducted a prospective randomized study of IV induction therapy versus a full year of high-dose IFN, with primary end points of RFS and OS for patients with stage IIB, IIC, and III melanoma, within 56 days of curative surgery. Patients were randomly assigned to receive IFN-alpha-2b 15 x 10(6) U/m2 IV x 5/7 days weekly x 4 weeks (arm A) versus the same regimen followed by IFN-alpha-2b 10 x 10(6) U (flat dose) administered subcutaneously three times a week for 48 weeks (arm B).


RESULTS
Between 1998 and 2004, 364 patients were enrolled (353 eligible: arm A, n = 177; arm B, n = 176). At a median follow-up of 63 months (95% CI, 58.1 to 67.7), the median RFS was 24.1 months versus 27.9 months (P = .9) and the median OS was 64.4 months versus 65.3 months (P = .49). Patients in arm B had more grade 1 to 2 hepatotoxicity, nausea/vomiting, alopecia, and neurologic toxicity.


CONCLUSIONS
There were no significant differences in OS and RFS between the regimens of 1 month and 1 year of treatment.
Pectasides
Dimitrios
D
Second Department of Internal Medicine-Propaedeutic, Oncology Section, University General Hospital Attikon, Athens, Greece.
Dafni
Urania
U
Bafaloukos
Dimitrios
D
Skarlos
Dimosthenis
D
Polyzos
Aristidis
A
Tsoutsos
Dimosthenis
D
Kalofonos
Haralambos
H
Fountzilas
George
G
Panagiotou
Petros
P
Kokkalis
George
G
Papadopoulos
Othon
O
Castana
Ourania
O
Papadopoulos
Stefanos
S
Stavrinidis
Elias
E
Vourli
Georgia
G
Ioannovich
John
J
Gogas
Helen
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000601:surgery; D008875:Middle Aged; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000601:surgery; D016019:Survival Analysis; D013997:Time Factors
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins