title: Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer.
abstract: BACKGROUND
  Cellular immune suppression is observed in head and neck squamous cell cancer (HNSCC) and contributes to poor prognosis. Restoration of immune homeostasis may require primary cell-derived cytokines at physiologic doses. An immunotherapy regimen containing a biologic, with multiple-active cytokine components, and administered with cytoxan, zinc, and indomethacin was developed to modulate cellular immunity.
  
  
  METHODS
  Study methods were designed to determine the safety and efficacy of a 21-day neoadjuvant immunotherapy regimen in a phase 2 trial that enrolled 27 therapy-naïve patients with stage II to IVa HNSCC. Methods included safety, clinical and radiologic tumor response, disease-free survival (DFS), overall survival (OS), and tumor lymphocytic infiltrate (LI) data collection.
  
  
  RESULTS
  Acute toxicity was minimal. Patients completed neoadjuvant treatment without surgical delay. By independent radiographic review, 83% had stable disease during treatment. OS was 92%, 73%, and 69% at 12, 24, and 36 months, respectively. Histologic analysis suggested correlation between survival and tumor LI.
  
  
  CONCLUSIONS
  Immunotherapy regimen was tolerated. Survival results are encouraging.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, Michigan, USA. gregwolf@umich.edu
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.forename: Willard E
authors.initials: WE
authors.lastname: Fee
authors.forename: Robert W
authors.initials: RW
authors.lastname: Dolan
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Moyer
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kaplan
authors.forename: Paul M
authors.initials: PM
authors.lastname: Spring
authors.forename: James
authors.initials: J
authors.lastname: Suen
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kenady
authors.forename: Jason G
authors.initials: JG
authors.lastname: Newman
authors.forename: William R
authors.initials: WR
authors.lastname: Carroll
authors.forename: M Boyd
authors.initials: MB
authors.lastname: Gillespie
authors.forename: Scott M
authors.initials: SM
authors.lastname: Freeman
authors.forename: Lorraine
authors.initials: L
authors.lastname: Baltzer
authors.forename: Terry D
authors.initials: TD
authors.lastname: Kirkley
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Brandwein
authors.forename: John W
authors.initials: JW
authors.lastname: Hadden
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D016207:Cytokines / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005942:Gluconates / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007213:Indomethacin / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage; D053583:Interleukin-1beta / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D005942:Gluconates; C114857:IRX 2; D053583:Interleukin-1beta; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003520:Cyclophosphamide; C030691:gluconic acid; D007213:Indomethacin