Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer

Head Neck. 2011 Dec;33(12):1666-74. doi: 10.1002/hed.21660. Epub 2011 Jan 31.

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.

Conclusion: Immunotherapy regimen was tolerated. Survival results are encouraging.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Cyclophosphamide / administration & dosage
  • Cytokines / therapeutic use*
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Gluconates / administration & dosage
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Immunotherapy*
  • Indomethacin / administration & dosage
  • Injections, Subcutaneous
  • Interferon-gamma / administration & dosage
  • Interleukin-1beta / administration & dosage
  • Interleukin-2 / administration & dosage
  • Male
  • Middle Aged
  • Neoadjuvant Therapy*
  • Survival Rate
  • Tumor Necrosis Factor-alpha / administration & dosage

Substances

  • Antineoplastic Agents
  • Cytokines
  • Gluconates
  • IRX 2
  • Interleukin-1beta
  • Interleukin-2
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Cyclophosphamide
  • gluconic acid
  • Indomethacin