Randomized trial of vitamin A versus observation as adjuvant therapy in high-risk primary malignant melanoma: a Southwest Oncology Group study.
OBJECTIVE
A national cooperative group trial was conducted in patients with early-stage cutaneous malignant melanoma to determine if oral vitamin A can increase disease-free survival or survival.


METHODS
Two hundred forty-eight patients with completely resected melanoma of Breslow's thickness greater than 0.75 mm and clinically negative lymph nodes were randomized to oral vitamin A (100,000 IU/d) for 18 months or to observation. Patients were stratified by Breslow's thickness of primary lesion (0.76 to 1.50 mm, 1.51 to 3.00 mm, or > 3.00 mm), sex, and type of therapy (excision, excision plus node dissection, excision plus perfusion, or excision plus both). The median duration of follow-up observation of living patients is greater than 8 years. The relative risk (RR) in disease-free survival and overall survival in the treatment compared with the observation group was calculated using Cox proportional hazards models.


RESULTS
Overall, there was no difference in disease-free survival or overall survival between the two groups. Examination of treatment by stratification interactions and subset analysis did not show any treatment-effect differences based on sex or type of therapy. There was also no difference between groups in disease-free survival based on Breslow's thickness of the primary lesion. Overall, 12% of patients who received vitamin A experienced grade 3 or 4 toxicities.


CONCLUSIONS
Based on the lack of overall survival benefit, further evaluation of vitamin A as adjuvant therapy for melanoma does not appear warranted.
Meyskens
F L
FL
University of California, Irvine, Orange.
Liu
P Y
PY
Tuthill
R J
RJ
Sondak
V K
VK
Fletcher
W S
WS
Jewell
W R
WR
Samlowski
W
W
Balcerzak
S P
SP
Rector
D J
DJ
Noyes
R D
RD
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D015996:Survival Rate; D014481:United States; D014801:Vitamin A / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D014801:Vitamin A