title: HspE7 treatment of pediatric recurrent respiratory papillomatosis: final results of an open-label trial.
abstract: OBJECTIVE
  We sought to evaluate the effectiveness of HspE7, a recombinant fusion protein of Hsp65 from Mycobacterium bovis BCG and E7 protein from human papillomavirus 16, to improve the clinical course of pediatric patients with recurrent respiratory papillomatosis.
  
  
  METHODS
  An open-label, single-arm intervention study was conducted in 8 university-affiliated medical centers. Twenty-seven male and female patients with recurrent respiratory papillomatosis, ages 2 to 18 years, were enrolled and followed up to 60 weeks. Before enrollment, these patients required surgery on average every 55 days. After a baseline debulking surgery, the patients received HspE7 500 microg subcutaneously monthly, for 3 doses over 60 days. The primary end point was the length of the interval from the last surgery during the treatment period until the first debulking surgery in the posttreatment period, compared with the median intersurgical interval (ISI) of the 4 surgeries before the treatment.
  
  
  RESULTS
  The mean of the first posttreatment ISI increased 93% (from 55 days to 106 days; p < .02). The median ISI for all surgeries after treatment was similarly prolonged (mean, 107 days; p < .02), indicating a sustained treatment effect, and was associated with a significant decrease in the number of required surgeries (p < .003). Unexpectedly, the treatment effect was most striking in the 13 female patients, who had statistically significant increases in both the first posttreatment ISI (142%; p < .03) and the median ISI (147%; p < .03). The most common adverse events were mild-to-moderate injection site reactions.
  
  
  CONCLUSIONS
  Treatment with HspE7 appears to significantly improve the clinical course in pediatric patients with RRP insofar as it reduces the frequency of required surgeries. These results warrant a confirmatory phase III trial.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Eastern Virginia Medical School, Norfolk, Virginia, USA.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Derkay
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: John
authors.initials: J
authors.lastname: McClay
authors.forename: Jo-Anne H
authors.initials: JA
authors.lastname: van Burik
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Wiatrak
authors.forename: James
authors.initials: J
authors.lastname: Arnold
authors.forename: Bruce
authors.initials: B
authors.lastname: Berger
authors.forename: John R
authors.initials: JR
authors.lastname: Neefe
mesh_terms: D000293:Adolescent; D001426:Bacterial Proteins / Q000235:genetics / Q000627:therapeutic use*; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000627:therapeutic use*; D010212:Papilloma / Q000188:drug therapy*; D027383:Papillomaviridae / Q000187:drug effects; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012142:Respiratory Tract Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; C074119:heat-shock protein 65, Mycobacterium; C059731:oncogene protein E7, Human papillomavirus type 16; D018833:Chaperonins