Phase III study of adjuvant vaccination with Bec2/bacille Calmette-Guerin in responding patients with limited-disease small-cell lung cancer (European Organisation for Research and Treatment of Cancer 08971-08971B; Silva Study)

J Clin Oncol. 2005 Oct 1;23(28):6854-64. doi: 10.1200/JCO.2005.17.186.

Abstract

Purpose: Bec2 is an anti-idiotypic antibody that mimics GD3, a ganglioside that is expressed on the surface of tumor cells and is of neuroectodermal origin. We assessed whether Bec2/bacille Calmette-Guerin (BCG) vaccination prolongs survival in patients with limited-disease small-cell lung cancer (SCLC) after a major response to chemotherapy and chest radiation.

Patients and methods: Patients were randomly assigned to receive five vaccinations of Bec2 (2.5 mg)/BCG vaccine or follow-up. Vaccination was given over a 10-week period. The sample size was targeted to detect an increase in median survival of 40% after random assignment, and stratification was by performance status, response, and institution. Quality of life was assessed by using the European Organisation for Research and Treatment of Cancer instrument. Humoral response was assessed in patients who received vaccination.

Results: A total of 515 patients were randomly assigned. The primary toxicities of vaccination were transient skin ulcerations and mild flu-like symptoms. There was no improvement in survival, progression-free survival, or quality of life in the vaccination arm. Median survival from randomization was 16.4 and 14.3 months in the observation and vaccination arms (P = .28), respectively. Among vaccinated patients, a trend toward prolonged survival was observed in those (one third) who developed a humoral response (P = .085). Multivariate analysis showed a positive impact on survival by prior treatment with concomitant chemoradiotherapy, prophylactic cranial irradiation, female sex, low lactate dehydrogenase, and normal platelets.

Conclusion: Vaccination with Bec2/BCG has no impact on outcome of patients with limited-disease SCLC responding to combined-modality treatment. Vaccination strategies in SCLC may still be warranted using vaccines that produce a better immunologic response.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibody Formation
  • BCG Vaccine / therapeutic use*
  • Carcinoma, Small Cell / drug therapy*
  • Carcinoma, Small Cell / surgery
  • Disease-Free Survival
  • Drug Administration Schedule
  • Ether-A-Go-Go Potassium Channels
  • Female
  • Humans
  • Immunotherapy
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / immunology*
  • Potassium Channels, Voltage-Gated / immunology*
  • Quality of Life

Substances

  • Adjuvants, Immunologic
  • BCG Vaccine
  • Ether-A-Go-Go Potassium Channels
  • KCNH4 protein, human
  • Nerve Tissue Proteins
  • Potassium Channels, Voltage-Gated