Randomised trial to identify the safest and most effective selenium compound for cancer patients

INTERVENTION: Arm 1: sodium selenite taken orally at doses of 400, 1600 or 6400 mcg elemental selenium daily for eight weeks Arm 2: L‐selenomethionine taken orally at doses of 400, 1600 or 6400 mcg elemental selenium daily for eight weeks Arm 3: Se‐methyl‐selenocysteine taken orally at doses of 400, 1600 or 6400 mcg elemental selenium daily for eight weeks The 3 dose levels within each arm represent separate cohorts. CONDITION: Cancer PRIMARY OUTCOME: Safety and tolerability of each selenium compound at the evaluated doses as assessed by compliance with study medication and occurrence of adverse events (graded using CTCAE version 4) on clinical, laboratory and electrocardiographic assessments SECONDARY OUTCOME: Dose‐response of the three selenium compounds with respect to pharmacodynamic markers: ; 1. endoplasmic reticulum stress response assessed by western blotting in peripheral blood mononuclear cells ; 2. DNA damage assessed by COMET assay in peripheral blood mononuclear cells ; 3. angiogenesis assessed by plasma ELISA assay ; 4. plasma glutathione peroxidase activity assessed by colorimetric assay ; 5. intracellular glutathione concentrations in peripheral blood mononuclear cells assessed by colorimetric assay ; ; Plasma concentrations of selenium achieved with oral administration of the three selenium compounds at each dose Speciation of selenium compounds in plasma, urine and peripheral blood mononuclear cells using various chromatography and mass spectrometry methods The relationship between dose, plasma selenium concentrations and pharmacodynamic markers of each compound in normal and malignant peripheral blood mononuclear cells Tumour response as assessed by serum tumour markers (where relevant) in cancer patients and peripheral blood counts of atypical lymphocytes in patients with chronic lymphocytic leukaemia INCLUSION CRITERIA: 1. Subjects with either chronic lymphocytic leukaemia (peripheral blood lymphocyte count > 10 x 10^9/l) or metastatic cancer, in whom the use of chemotherapy is not anticipated in the next 3 months 2. Adequate liver, renal and bone marrow function 3. ECOG performance status 0‐2 4. Life expectancy over 6 months