title: 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).
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Medical Oncology, Vrije Universiteit Medical Center, 1117 De Boelelaan, Amsterdam, the Netherlands. g.giaccone@vumc.nl
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
authors.forename: Channa
authors.initials: C
authors.lastname: Debruyne
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.forename: Paul B
authors.initials: PB
authors.lastname: Chapman
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Grant
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
authors.forename: Luc
authors.initials: L
authors.lastname: Thiberville
authors.forename: Giannicola
authors.initials: G
authors.lastname: D'addario
authors.forename: Corneel
authors.initials: C
authors.lastname: Coens
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Rome
authors.forename: Petr
authors.initials: P
authors.lastname: Zatloukal
authors.forename: Oriol
authors.initials: O
authors.lastname: Masso
authors.forename: Catherine
authors.initials: C
authors.lastname: Legrand
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation; D001500:BCG Vaccine / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000601:surgery; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology*; D024642:Potassium Channels, Voltage-Gated / Q000276:immunology*; D011788:Quality of Life
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D051638:Ether-A-Go-Go Potassium Channels; C121382:KCNH4 protein, human; D009419:Nerve Tissue Proteins; D024642:Potassium Channels, Voltage-Gated