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Biological Trace Element Research

, Volume 189, Issue 2, pp 395–404 | Cite as

Comparative Safety and Pharmacokinetic Evaluation of Three Oral Selenium Compounds in Cancer Patients

  • Stephen O. Evans
  • Gregory M. Jacobson
  • Hugh J. B. Goodman
  • Steve Bird
  • Michael B. JamesonEmail author
Article

Abstract

Selenium (Se) compounds have demonstrated anticancer properties in both preclinical and clinical studies, with particular promise in combination therapy where the optimal form and dose of selenium has yet to be established. In a phase I randomised double-blinded study, the safety, tolerability and pharmacokinetic (PK) profiles of sodium selenite (SS), Se-methylselenocysteine (MSC) and seleno-l-methionine (SLM) were compared in patients with chronic lymphocytic leukaemia and a cohort of patients with solid malignancies. Twenty-four patients received 400 μg of elemental Se as either SS, MSC or SLM for 8 weeks. None of the Se compounds were associated with any significant toxicities, and the total plasma Se AUC of SLM was markedly raised in comparison to MSC and SS. DNA damage assessment revealed negligible genotoxicity, and some minor reductions in lymphocyte counts were observed. At the dose level used, all three Se compounds are well-tolerated and non-genotoxic. Further analyses of the pharmacodynamic effects of Se on healthy and malignant peripheral blood mononuclear cells will inform the future evaluation of higher doses of these Se compounds. The study is registered under the Australian and New Zealand Clinical Trials Registry No: ACTRN12613000118707.

Keywords

Selenium Pharmacokinetics Clinical trial Methylselenocysteine Cancer Chronic lymphocytic leukaemia Double-blinded 

Notes

Acknowledgements

We thank all the patients and families who participated in this study.

Authors’ Contributions

SOE contributed to study design, sample collection, performed the experiments, analysed the data and wrote the manuscript. GMJ contributed to experimental design, laboratory experiments and contributed to the manuscript. SB contributed to experimental design and contributed to the manuscript. HJBG contributed to study conduct, patient assessment and to the manuscript. MBJ, as study PI, conceived the project, wrote the trial protocol, oversaw the clinical and experimental aspects of the study (including patient assessment), assisted with data collection, analysis and interpretation and co-wrote the study manuscript.

Funding

Funding sources (Waikato Medical Research Foundation, Genesis Oncology Trust, Cycle for Life).

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.

Ethics Approval

Ethical approval was obtained through Northern A Health and Disability Ethics Committee (HDEC) (13/NTA/172). All procedures performed in this study were in accordance with the ethical standards of the Waikato DHB research committee and HDEC and with the 1964 Declaration of Helsinki and its later amendments.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12011_2018_1501_MOESM1_ESM.docx (474 kb)
ESM 1 (DOCX 474 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biological SciencesUniversity of WaikatoHamiltonNew Zealand
  2. 2.Waikato Clinical CampusUniversity of AucklandHamiltonNew Zealand
  3. 3.Regional Cancer CentreWaikato HospitalHamiltonNew Zealand

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