Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3

Cancer Immunol Immunother. 2004 May;53(5):422-30. doi: 10.1007/s00262-003-0459-7. Epub 2003 Nov 26.


Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune defects. These defects are associated with a poor prognosis and are mediated, in part, by immune inhibitory CD34(+) progenitor cells, whose numbers are increased in the peripheral blood of HNSCC patients. Immune inhibitory CD34(+) cells are also present within HNSCC tumors. A phase IB clinical trial was conducted with HNSCC patients to determine if treatment with the differentiation-inducer 25-hydroxyvitamin D(3) could diminish CD34(+) cell levels and improve a panel of immune parameters. Here we present the results of treatment with orally administered escalating doses (20, 40, 60 microg) of 25-hydroxyvitamin D(3), with an emphasis on the six patients who received the maximum dosage of 60 microg per day. Peripheral blood was collected at 0, 1, 2, 4, and 6 weeks, and assessed for markers of immune activity. Although no clinical responses were observed, results of this pilot study demonstrated that treatment of HNSCC patients with 25-hydroxyvitamin D(3 )reduces the number of immune suppressive CD34(+) cells, increases HLA-DR expression, increases plasma IL-12 and IFN-gamma levels, and improves T-cell blastogenesis. In contrast, 25-hydroxyvitamin D(3) treatment did not modulate plasma IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, or TGF-beta levels.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Antigens, CD34 / analysis
  • Calcifediol / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / immunology
  • Cytokines / blood*
  • Female
  • HLA-DR Antigens / analysis
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / immunology
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology


  • Antigens, CD34
  • Cytokines
  • HLA-DR Antigens
  • Calcifediol