title: Phase 1B study to improve immune responses in head and neck cancer patients using escalating doses of 25-hydroxyvitamin D3.
abstract: 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.
authors.affiliation: Research Service (151), Ralph H. Johnson Veterans Affairs Medical Center, 109 Bee Street, SC 29401-5799, Charleston, USA.
authors.forename: Deanne M R
authors.initials: DM
authors.lastname: Lathers
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Clark
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Achille
authors.forename: M Rita I
authors.initials: MR
authors.lastname: Young
mesh_terms: D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D002112:Calcifediol / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D006684:HLA-DR Antigens; D002112:Calcifediol