Randomized trial of an allogeneic melanoma lysate vaccine with low-dose interferon Alfa-2b compared with high-dose interferon Alfa-2b for Resected stage III cutaneous melanoma.
OBJECTIVE
To compare the overall survival (OS) of patients with resected stage III melanoma administered active specific immunotherapy and low-dose interferon alfa-2b (IFN-alpha-2b) with the OS achieved using high-dose IFN-alpha-2b.


METHODS
An Ad Hoc Melanoma Working Group of 25 investigators treated 604 patients from April 1997 to January 2003. Patients were stratified by sex and number of nodes and were randomly assigned to receive either 2 years of treatment with active specific immunotherapy with allogeneic melanoma lysates and low-dose IFN-alpha-2b (arm 1) or high-dose IFN-alpha-2b alone for 1 year (arm 2). Active specific immunotherapy was injected subcutaneously (SC) weekly for 4 weeks, at week 8, and bimonthly thereafter. IFN-alpha-2b SC was begun on week 4 and continued thrice weekly at 5 MU/m2 for 2 years. IFN-alpha-2b in arm 2 was administered according to the Eastern Cooperative Oncology Group 1684 study regimen.


RESULTS
Median follow-up time was 32 months for all patients and 42 months for surviving patients. Median OS time exceeds 84 months in arm 1 and is 83 months in arm 2 (P = .56). Five-year OS rate is 61% in arm 1 and 57% in arm 2. Estimated 5-year relapse-free survival (RFS) rate is 50% in arm 1 and 48% in arm 2, with median RFS times of 58 and 50 months, respectively. The incidence of serious adverse events as a result of treatment was the same in both arms, but more severe neuropsychiatric toxicity was seen in arm 2.


CONCLUSIONS
OS and RFS achieved by active specific immunotherapy and low-dose IFN-alpha-2b were indistinguishable from those achieved by high-dose IFN-alpha-2b. Long RFS and OS times were observed in both treatment arms.
Mitchell
Malcolm S
MS
University of California, San Diego, School of Medicine and Cancer Center, San Diego, CA, USA. malcolmsmitchell@yahoo.com
Abrams
Judith
J
Thompson
John A
JA
Kashani-Sabet
Mohammed
M
DeConti
Ronald C
RC
Hwu
Wen-Jen
WJ
Atkins
Michael B
MB
Whitman
Eric
E
Ernstoff
Marc S
MS
Haluska
Frank G
FG
Jakowatz
James G
JG
Das Gupta
Tapas K
TK
Richards
Jon M
JM
Samlowski
Wolfram E
WE
Costanzi
John J
JJ
Aronson
Frederick R
FR
Deisseroth
Albert B
AB
Dudek
Arkadiusz Z
AZ
Jones
Vicky E
VE
D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003598:Cytoskeletal Proteins; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016233:Immunotherapy, Active; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008050:Lipid A / Q000031:analogs & derivatives; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate
D019496:Cancer Vaccines; D003598:Cytoskeletal Proteins; D004338:Drug Combinations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008050:Lipid A; C116434:Melacine; D011994:Recombinant Proteins; C112124:detox adjuvant