Journal article
A phase I and pharmacokinetic study of fixed-dose selenomethionine and irinotecan in solid tumors
Clinical cancer research, Vol.12(4), pp.1237-1244
2006
DOI: 10.1158/1078-0432.CCR-05-2004
PMID: 16489079
Abstract
Purpose: We conducted a phase I study to determine the maximum tolerated dose (MTD) of irinotecan with fixed, nontoxic high dose of selenomethionine. Experimental Design: Selenomethionine was given orally as a single daily dose containing 2,200 μg of elemental selenium (Se) starting 1 week before the first dose of irinotecan. Irinotecan was given i.v. once weekly × 4 every 6 weeks (one cycle). The starting dose of irinotecan was 125 mg/m 2/wk. Escalation occurred in cohorts of three patients until the MTD was defined. Pharmacokinetic studies were done for selenium and irinotecan and its metabolites. Results: Three of four evaluable patients at dose level 2 of irinotecan (160 mg/m2/wk) had a dose-limiting diarrhea. None of the six evaluable patients at dose level 1 (125 mg/m2/wk irinotecan) had a dose-limiting toxicity. One patient with history of irinotecan-refractory colon cancer achieved a partial response. The long half-life of selenium resulted in a prolonged accumulation towards steady-state concentrations. No significant changes in the pharmacokinetics of CPT-11, SN-38, or SN-38G were identified; however, the coadministration of selenomethionine significantly reduced the irinotecan biliary index, which has been associated with gastrointestinal toxicity. Conclusions: Selenomethionine at 2,200 μg/d did not allow the safe escalation of irinotecan beyond the previously defined MTD of 125 mg/m2. None of the patients receiving 125 mg/m2 of irinotecan had grade >2 diarrhea. Unexpected responses and disease stabilizations were noted in a highly refractory population. Further escalation of selenomethionine is recommended in future trials to achieve defined protective serum concentrations of selenium. © 2006 American Association for Cancer Research.
Details
- Title: Subtitle
- A phase I and pharmacokinetic study of fixed-dose selenomethionine and irinotecan in solid tumors
- Creators
- Marwan G Fakih - Roswell Park Cancer InstituteLakshmi Pendyala - Roswell Park Cancer InstitutePatrick F Smith - Roswell Park Cancer InstitutePatrick J Creaven - Roswell Park Cancer InstituteMary E Reid - Roswell Park Cancer InstituteVladimir Badmaev - Sabinsa Pharmaceutical, Inc, Piscataway, New Jersey, United StatesRami G Azrak - Roswell Park Cancer InstituteJoshua D Prey - Roswell Park Cancer InstituteDavid Lawrence - Roswell Park Cancer InstituteYoucef M Rustum - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.12(4), pp.1237-1244
- Publisher
- American Association for Cancer Research
- DOI
- 10.1158/1078-0432.CCR-05-2004
- PMID
- 16489079
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Language
- English
- Date published
- 2006
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359670002771
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