title: A phase 2 trial of surgery with perioperative INGN 201 (Ad5CMV-p53) gene therapy followed by chemoradiotherapy for advanced, resectable squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx: report of the Southwest Oncology Group.
abstract: OBJECTIVE
  To assess the feasibility of treating patients with high-risk stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx with perioperative adenovirus-p53 (INGN 201) gene therapy along with surgery and chemoradiotherapy.
  
  
  METHODS
  A phase 2 study in a multi-institutional setting within the Southwest Oncology Group.
  
  
  METHODS
  Thirteen individuals who met the following entry criteria: newly diagnosed, previously untreated squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx; selected stage III or IV disease without distant metastases; and surgically resectable disease.
  
  
  METHODS
  Surgery, perioperative INGN 201 gene therapy, and postoperative chemoradiotherapy.
  
  
  METHODS
  Overall patient status, tumor status, adverse effects, accrual rate, and percentage of patients successfully receiving the required doses of INGN 201.
  
  
  RESULTS
  All 13 patients received surgery and perioperative INGN 201 injections in the primary tumor bed and the ipsilateral neck. In addition, 3 patients received injections in the contralateral neck. Three patients did not receive chemoradiotherapy. One patient had a grade 2 fistula of the oral cavity. Of the 10 patients with evaluable data, 2 experienced grade 4 adverse events, 1 owing to hypokalemia, hyponatremia, vomiting, leukopenia, and neutropenia and 1 owing to increased aspartate aminotransferase and alanine aminotransferase levels. Seven other patients experienced grade 3 adverse events. The estimate of 1-year progression-free survival is 92%.
  
  
  CONCLUSIONS
  This trial demonstrated the feasibility of handling and delivering a very complex gene vector safely in multiple cooperative group institutions without significant incident. Intraoperative INGN 201 gene therapy is technically feasible, but it has many logistical problems when performed in a multi-institutional setting. Regulatory requirements might have hindered accrual in this multi-institutional setting. Disease control seems to be promising; however, no definitive conclusion can be made with this small sample size.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00017173.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Wayne State University, University Health Center 5-E, 4201 St Antoine, Detroit, MI 48201, USA.
authors.forename: George H
authors.initials: GH
authors.lastname: Yoo
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.forename: Michael
authors.initials: M
authors.lastname: Leblanc
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lonardo
authors.forename: Susan
authors.initials: S
authors.lastname: Urba
authors.forename: Harold
authors.initials: H
authors.lastname: Kim
authors.forename: Ehab
authors.initials: E
authors.lastname: Hanna
authors.forename: Terry
authors.initials: T
authors.lastname: Tsue
authors.forename: Joseph
authors.initials: J
authors.lastname: Valentino
authors.forename: John
authors.initials: J
authors.lastname: Ensley
authors.forename: Gregory
authors.initials: G
authors.lastname: Wolf
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007013:Hypopharynx / Q000473:pathology / Q000601:surgery; D015552:Injections, Intralesional; D007822:Laryngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D007830:Larynx / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009055:Mouth / Q000473:pathology / Q000601:surgery; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D009960:Oropharynx / Q000473:pathology / Q000601:surgery; D018579:Patient Selection; D019990:Perioperative Care / Q000379:methods; D011336:Probability; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D014765:Viral Vaccines / Q000627:therapeutic use*
chemical_list: D014765:Viral Vaccines; C512972:advexin