title: Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC.
  
  
  METHODS
  Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53.
  
  
  RESULTS
  Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum.
  
  
  CONCLUSIONS
  Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.
authors.affiliation: Department of Head and Neck Surgery, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. gclayman@notes.mdacc.tmc.edu
authors.forename: G L
authors.initials: GL
authors.lastname: Clayman
authors.forename: A K
authors.initials: AK
authors.lastname: el-Naggar
authors.forename: S M
authors.initials: SM
authors.lastname: Lippman
authors.forename: Y C
authors.initials: YC
authors.lastname: Henderson
authors.forename: M
authors.initials: M
authors.lastname: Frederick
authors.forename: J A
authors.initials: JA
authors.lastname: Merritt
authors.forename: L A
authors.initials: LA
authors.lastname: Zumstein
authors.forename: T M
authors.initials: TM
authors.lastname: Timmons
authors.forename: T J
authors.initials: TJ
authors.lastname: Liu
authors.forename: L
authors.initials: L
authors.lastname: Ginsberg
authors.forename: J A
authors.initials: JA
authors.lastname: Roth
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
authors.forename: P
authors.initials: P
authors.lastname: Bruso
authors.forename: H
authors.initials: H
authors.lastname: Goepfert
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000628:therapy*; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques / Q000009:adverse effects; D005822:Genetic Vectors / Q000008:administration & dosage / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53