title: A phase III randomized, double-blind multiinstitutional trial of vaccinia melanoma oncolysate-active specific immunotherapy for patients with stage II melanoma.
abstract: BACKGROUND
  In a Phase II trial, surgical adjuvant active specific immunotherapy using a live vaccinia virus-augmented allogeneic polyvalent melanoma cell lysate, vaccinia melanoma oncolysate (VMO), produced a significant disease free interval (DFI) in patients with International Union Against Cancer Stage II melanoma with positive lymph nodes. Therefore, a Phase III randomized prospective, double-blind, multiinstitutional, surgical adjuvant VMO trial was performed to determine the efficacy of VMO to increase the DFI and the overall survival in this group of patients with Stage II disease.
  
  
  METHODS
  Two hundred and fifty patients with Stage II melanoma were divided into two postsurgical groups. One group received VMO (total protein equals 2 mg/ml) and the other received the placebo of live vaccinia vaccine virus (V) (10(5.4) TCID50/ml), an adjuvant component of the VMO. Patients initially received these biologics once a week for 13 weeks and then once every 2 weeks for an additional 39 weeks or until recurrence. All surviving patients have been followed for at least 30 months.
  
  
  RESULTS
  Statistical analysis of survival data (n = 217) for this first interim analysis shows that there is no statistically significant (P = 0.99) increase in DFI of patients treated with VMO (n = 104) when compared with V (n = 113). The median DFI is 38.0 months for patients treated with VMO and 37.0 months for patients treated with V. At 2- and 4-year intervals, 70 and 38%, respectively, of patients treated with VMO vs. 66 and 36%, respectively, of patients treated with V were free of melanoma. The median overall survival is not available because the patients treated with VMO have not yet reached the 50% mark and the median overall survival is 45.0 months for patients treated with V. At 2- and 4-year intervals, 70 and 38%, respectively, of VMO-treated patients survived when compared with 66 and 36%, respectively, of patients treated with V. Although the overall survival of patients treated with VMO is not statistically significant (P = 0.88) at this point, there is an increasing trend in the overall survival of patients treated with VMO; a 10% increase at the 4-year time point. Moreover, in the subset analysis, VMO-treated male patients (n = 63) showed a 17% improvement in survival at 4-year time point when compared with male patients treated with V (n = 67) (P = 0.19) at the same time point and male patients (n = 20) between the ages of 44 and 57 having 1-5 positive lymph nodes showed a 37% difference in overall survival at the 4-year time point when compared with those patients treated with V (n = 18) (P = 0.13) at the same time point.
  
  
  CONCLUSIONS
  In this first interim analysis, active specific immunotherapy with VMO vs. V showed no difference in the disease free interval or overall survival. Subset analyses likewise showed no significant differences in outcome but the data suggest a potential difference in immunoreactivity between male and female patients with melanoma that awaits further follow up and may merit further investigation.
authors: St. Vincent's Hospital and Medical Center of New York, New York.
authors: M K
authors: MK
authors: Wallack
authors: M
authors: M
authors: Sivanandham
authors: C M
authors: CM
authors: Balch
authors: M M
authors: MM
authors: Urist
authors: K I
authors: KI
authors: Bland
authors: D
authors: D
authors: Murray
authors: W A
authors: WA
authors: Robinson
authors: L E
authors: LE
authors: Flaherty
authors: J M
authors: JM
authors: Richards
authors: A A
authors: AA
authors: Bartolucci
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000627:therapeutic use; D017778:Vaccines, Combined / Q000009:adverse effects / Q000627:therapeutic use; D014616:Vaccinia virus / Q000276:immunology*; D014765:Viral Vaccines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000951:Antigens, Neoplasm; D014613:Vaccines, Attenuated; D017778:Vaccines, Combined; D014765:Viral Vaccines