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

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.

The Interaction of Selenium with Chemotherapy and Radiation on Normal and Malignant Human Mononuclear Blood Cells

“…It is possible that higher doses of Se might safely be used with some chemotherapy drugs. It is noteworthy that dosing to achieve plasma Se levels determined by this in vitro study would not apply to seleno-l-methionine, as it is non-specifically incorporated into the general protein pool, especially albumin, which gives disproportionately high plasma Se levels compared to dosing with equivalent elemental Se doses of sodium selenite or Se-methylselenocysteine [ 54 , 55 ].…”

Selenium Compounds as Novel Potential Anticancer Agents

“…Selenomethionine (L-selenomethionine, seleno-L-methionine, SeMet, Figure 10, structure 26) is the major selenoamino acid contained in Se-enriched yeasts [3], which has very low toxicity and is non-genotoxic [4,27,101]. Studies have indicated that the tissue accumulation of selenium was better when SeMet was ingested with the diet compared to other forms of selenium [5,27,101].…”

Selenium in cereals: Insight into species of the element from total amount

“…For Se utilization and Se‐protein synthesis, HSe – is phosphorylated by ATP to generate the Se‐donor selenophosphate (SePhp) (Turanov et al., 2011). The pharmacokinetic profiles of Se compounds revealed that SeMet contributed to greater systemic exposure than selenite and MeSeCys (Evans et al., 2019). Administration of SeMet resulted in higher levels of Se deposition in serum, liver, kidney, pancreas, and muscle than administration of selenite and Se‐enriched yeast in broiler breeders (Li et al., 2018).…”

“…The toxicities of Se compounds would be discussed in terms of excessive intake, and certain threshold intake concentrations of different compounds or Se forms need to be further investigated. Administration of 400 μg/day Se in the forms of selenite, MeSeCys, or SeMet for 8 weeks was well‐tolerated and nongenotoxic in cancer patients with chronic lymphocytic leukemia or metastatic solid malignancies (Evans et al., 2019). The excessive intake of Se showed clinical signs of Se toxicity in pigs, and the severity of Se toxicity was presented in the order Astragalus bisulcatus (nonprotein, water‐soluble plant forms of Se, with a small amount of swainsonine causing lesions) > selenate > SeMet (Panter et al., 1996).…”