Randomized trial of vitamin A versus observation as adjuvant therapy in high-risk primary malignant melanoma: a Southwest Oncology Group study

J Clin Oncol. 1994 Oct;12(10):2060-5. doi: 10.1200/JCO.1994.12.10.2060.


Purpose: 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.

Patients and 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.

Conclusion: Based on the lack of overall survival benefit, further evaluation of vitamin A as adjuvant therapy for melanoma does not appear warranted.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / mortality
  • Melanoma / surgery
  • Middle Aged
  • Proportional Hazards Models
  • Risk Factors
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / surgery
  • Survival Rate
  • United States
  • Vitamin A / administration & dosage
  • Vitamin A / adverse effects
  • Vitamin A / therapeutic use*


  • Vitamin A