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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 3/2008

01-08-2008 | Original Article

A Phase I and pharmacokinetic study of selenomethionine in combination with a fixed dose of irinotecan in solid tumors

Authors: Marwan G. Fakih, Lakshmi Pendyala, William Brady, Patrick F. Smith, Mary E. Ross, Patrick J. Creaven, Vladimir Badmaev, Joshua D. Prey, Youcef M. Rustum

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2008

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Abstract

Purpose

We conducted a phase I study to determine the recommended dose of selenomethionine (SLM) in combination with irinotecan that consistently results in a protective plasma selenium (Se) concentrations > 15 μM after 1 week of SLM loading.

Experimental Design

A 3-3 standard escalation design was followed. SLM was given orally twice daily (BID) for one week (loading) followed by continuous once daily (QD) dosing (maintenance). Seven dose levels of selenomethionine were investigated. Irinotecan was given intravenously at a fixed standard weekly dose, starting on the first day of maintenance SLM.

Results

Thirty-one patients were treated on study. Dose limiting diarrhea complicated by sepsis was noted in one of six patients at each of the dose-levels 1 and 7. Dose-levels ≥ 5 (4,800 mcg/dose loading maintenance) resulted in day 8 Se concentrations >15 μM while dose-level 7 (7,200 mcg/dose loading and maintenance) resulted in day 8 Se concentrations > 20 μM. No significant variations in SN-38 or biliary index were noted between weeks 1 and 4 of treatment. Despite achieving target Se concentrations, gastrointestinal and bone marrow toxicities were common and irinotecan dose modification was prevalent. Objective responses were seen in two patients and nine patients had disease control for 6 months or longer.

Conclusions

Selenomethionine can be escalated safely to 7,200 mcg BID × 1 week followed by 7,200 mcg QD in combination with a standard dose of irinotecan. No major protection against irinotecan toxicity was established; however, interesting clinical benefits were noted-supporting the investigation of this combination in future efficacy trials.
Literature
1.
Schrauzer GN, White DA, Schneider CJ (1977) Cancer mortality correlation studies-III: statistical associations with dietary selenium intakes. Bioinorg Chem 7(1):23–31PubMedCrossRef
2.
Clark LC, Cantor KP, Allaway WH (1991) Selenium in forage crops and cancer mortality in U.S. counties. Arch Environ Health 46(1):37–42PubMedCrossRef
3.
Helzlsouer KJ, Comstock GW, Morris JS (1989) Selenium, lycopene, alpha-tocopherol, beta-carotene, retinol, and subsequent bladder cancer. Cancer Res 49(21):6144–8PubMed
4.
Burney PG, Comstock GW, Morris JS (1989) Serologic precursors of cancer: serum micronutrients and the subsequent risk of pancreatic cancer. Am J Clin Nutr 49(5):895–900PubMed
5.
Glattre E et al (1989) Prediagnostic serum selenium in a case-control study of thyroid cancer. Int J Epidemiol 18(1):45–9PubMedCrossRef
6.
Jaskiewicz K et al (1988) Selenium and other mineral elements in populations at risk for esophageal cancer. Cancer 62(12):2635–9PubMedCrossRef
7.
Gerhardsson L et al (1985) Protective effect of selenium on lung cancer in smelter workers. Br J Ind Med 42(9):617–26PubMed
8.
Miyamoto H et al (1987) Serum selenium and vitamin E concentrations in families of lung cancer patients. Cancer 60(5):1159–62PubMedCrossRef
9.
Reinhold U et al (1989) Serum selenium levels in patients with malignant melanoma. Acta Derm Venereol 69(2):132–6PubMed
10.
Westin T et al (1989) Circulating levels of selenium and zinc in relation to nutritional status in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 115(9):1079–82PubMed
11.
Criqui MH et al (1991) Selenium, retinol, retinol-binding protein, and uric acid. Associations with cancer mortality in a population-based prospective case-control study. Ann Epidemiol 1(5):385–93PubMedCrossRef
12.
Hardell L et al (1995) Levels of selenium in plasma and glutathione peroxidase in erythrocytes in patients with prostate cancer or benign hyperplasia. Eur J Cancer Prev 4(1):91–5PubMedCrossRef
13.
Clark LC et al (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Jama 276(24):1957–63PubMedCrossRef
14.
Duffield-Lillico AJ et al (2003) Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst 95(19):1477–81PubMed
15.
Last KW et al (2003) Presentation serum selenium predicts for overall survival, dose delivery, and first treatment response in aggressive non-Hodgkin’s lymphoma. J Clin Oncol 21(12):2335–41PubMedCrossRef
16.
Cao S, Durrani FA, Rustum YM (2004) Selective modulation of the therapeutic efficacy of anticancer drugs by selenium containing compounds against human tumor xenografts. Clin Cancer Res 10(7):2561–9PubMedCrossRef
17.
Azrak RG et al (2007) Efficacy of increasing the therapeutic index of irinotecan, plasma and tissue selenium concentrations is methylselenocysteine dose dependent. Biochem Pharmacol 73(9):1280–7PubMedCrossRef
18.
Fakih M et al (2005) Selenium protects against toxicity induced by anticancer drugs and augments antitumor activity: a highly selective, new, and novel approach for the treatment of solid tumors. Clin Colorectal Cancer 5(2):132–5PubMedCrossRef
19.
Fakih MG et al (2006) A phase I and pharmacokinetic study of fixed-dose selenomethionine and irinotecan in solid tumors. Clin Cancer Res 12(4):1237–44PubMedCrossRef
20.
Rothenberg ML et al (1993) Phase I and pharmacokinetic trial of weekly CPT-11. J Clin Oncol 11(11):2194–204PubMed
21.
Therasse P et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92(3):205–16PubMedCrossRef
22.
Ip C (1998) Lessons from basic research in selenium and cancer prevention. J Nutr 128(11):1845–54PubMed
23.
Goulet AC et al (2007) Profiling of Selenomethionine Responsive Genes in Colon Cancer by Microarray Analysis. Cancer Biol Ther 6(4)
24.
Fischer JL et al (2007) Chemotherapeutic selectivity conferred by selenium: a role for p53–dependent DNA repair. Mol Cancer Ther 6(1):355–61PubMedCrossRef
25.
Zhao R, Domann FE, Zhong W (2006) Apoptosis induced by selenomethionine and methioninase is superoxide mediated and p53 dependent in human prostate cancer cells. Mol Cancer Ther 5(12):3275–84PubMedCrossRef
Metadata
Title
A Phase I and pharmacokinetic study of selenomethionine in combination with a fixed dose of irinotecan in solid tumors
Authors
Marwan G. Fakih
Lakshmi Pendyala
William Brady
Patrick F. Smith
Mary E. Ross
Patrick J. Creaven
Vladimir Badmaev
Joshua D. Prey
Youcef M. Rustum
Publication date
01-08-2008
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 3/2008
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-007-0631-4

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