Article Text

Download PDFPDF

Phase I study of alpha-tocopherlyoxyacetic acid in patients with advanced cancer
  1. Brendan D Curti1,
  2. Emmanuel Akporiaye2,
  3. Kim Sutcliffe3,
  4. Keith S Bahjat4,
  5. Yoshinobu Koguchi5,
  6. Julie Cramer3 and
  7. Walter Urba5
  1. Aff1 grid.240531.1000000040456863XProvidence Cancer CenterProvidence Portland Medical Center Portland OR USA
  2. Aff2 grid.467063.00000000403974222Sidra Medical and Research Center Doha Qatar
  3. Aff3 grid.240531.1000000040456863XProvidence Portland Medical Center Portland OR USA
  4. Aff4 grid.415337.7Earle A. Chiles Research Institute, Robert W. Franz Cancer Research CenterProvidence Cancer Center Portland OR USA
  5. Aff5 grid.415286.c0000 0004 0463 5556Earle A. Chiles Research Institute Portland OR USA

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Meeting abstracts

Alpha-tocopheryloxyacetic acid (α-TEA) is a pro-apoptotic agent that demonstrates in vivo anti-tumor activity in pre-clinical models in a T cell-dependent fashion. In IND-enabling studies, orally administered α-TEA lysine salt demonstrated a safety profile in mice and dogs providing rationale for initiating a Phase I clinical trial of α-TEA in patients with advanced cancer (NCT02192346). α-TEA lysine salt was administered to patients in gelatin capsules daily for 28 days. The main clinical objectives of the trial are to characterize α-TEA related toxicity, and determine the maximum tolerated dose, and pharmacokinetics of a-TEA in humans. Secondary objectives are to characterize the phenotype of T-cell subsets in the peripheral blood by flow cytometry. The diagnoses of patients in the ongoing trial include renal cancer, esophageal cancer, thyroid cancer, duodenal cancer, squamous cell oropharyngeal cancer and advanced squamous cell carcinoma of the head and neck. Six patients have been treated at the 2.4mg/kg dose level, and five patients at the 4.8mg/kg dose level. Two patients had atrial fibrillation possibly associated with α-TEA at the 4.8 mg/kg dose level. Grade 2/3 toxicities (24 hour diarrhea) were observed in Subject 1 that in retrospect was not α-TEA related. Subject 3 had grade 4 elevations of hepatocellular enzymes on day 28 from disease progression and grade 3 transient lymphopenia, possibly related to α-TEA. Three patients have stable disease, one lasting 5 months and another lasting 2+ months, which is ongoing. Of interest is that the two patients with stable disease demonstrated an expansion of the CD8+ T cell subset and another patient demonstrated increased CD8 effector memory and substantial increase in expression of the activation markers, CD38 and HLA-DR at day 8 post-treatment. The trial is still accruing patients and the pharmacokinetics, pharmacodynamics, and identification and characterization of α-TEA metabolites in human plasma are ongoing.

Trial registration identifier NCT02192346.


The study was supported by funds from The Safeway Foundation, Providence Portland Medical Center Foundation and The Heath Foundation.