Mature results of a phase III randomized trial of bacillus Calmette-Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer Stage I-III melanoma (E1673): a trial of the Eastern Oncology Group

Cancer. 2004 Apr 15;100(8):1692-8. doi: 10.1002/cncr.20166.

Abstract

Background: The local and systemic effects of bacillus Calmette-Guerin (BCG) have been known for decades. To investigate the adjuvant effect of BCG on resected American Joint Committee on Cancer (AJCC) Stage I-III melanoma, the Eastern Cooperative Oncology Group conducted a large trial to study the use of BCG alone or a combination of BCG and dacarbazine between 1974 and 1978.

Methods: A total of 734 patients were randomized to 4 clinical groups consolidated into 2 cohorts. Cohort I compared BCG with observation and Cohort II compared BCG with a combination of BCG and dacarbazine. The primary end points were survival time and time to disease progression.

Results: Within Cohort I, no statistically significant difference in disease-free survival (DFS) (P = 0.84) or overall survival (OS) (5-year survival 67% vs. 62%; P = 0.40) was observed between BCG treatment and observation. Within Cohort II, the addition of dacarbazine to BCG did not improve DFS (P = 0.74) or OS (P = 0.81) compared with BCG alone. Toxicity was mild to moderate in both cohorts. Although toxicity with this agent is mild, the use of BCG is associated with the development of punctate abscesses in greater than two-thirds of patients treated.

Conclusions: In what to our knowledge is the largest ever trial to test the role of BCG as adjuvant therapy for melanoma, no benefit for BCG was observed for patients with AJCC Stage I-III disease. The mature results of the current trial projected to 30 years confirmed the negative results of previous smaller studies utilizing this agent.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • BCG Vaccine / therapeutic use*
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Dacarbazine / administration & dosage
  • Dacarbazine / therapeutic use*
  • Disease Progression
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Survival Analysis
  • Treatment Outcome

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents, Alkylating
  • BCG Vaccine
  • Dacarbazine