Journal article
A Phase I and pharmacokinetic study of selenomethionine in combination with a fixed dose of irinotecan in solid tumors
Cancer chemotherapy and pharmacology, Vol.62(3), pp.499-508
08/01/2008
DOI: 10.1007/s00280-007-0631-4
PMID: 17989978
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 mu M after 1 week of SLM loading.
Experimental 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 mu M while dose-level 7 (7,200 mcg/dose loading and maintenance) resulted in day 8 Se concentrations > 20 mu M. 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 x 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.
Details
- Title: Subtitle
- A Phase I and pharmacokinetic study of selenomethionine in combination with a fixed dose of irinotecan in solid tumors
- Creators
- Marwan G. Fakih - Roswell Park Cancer InstituteLakshmi Pendyala - Roswell Park Cancer InstituteWilliam Brady - Roswell Park Cancer InstitutePatrick F. Smith - University at Buffalo, State University of New YorkMary E. Ross - Roswell Park Cancer InstitutePatrick J. Creaven - Roswell Park Cancer InstituteVladimir Badmaev - Sabin Vaccine InstituteJoshua D. Prey - Roswell Park Cancer InstituteYoucef M. Rustum - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.62(3), pp.499-508
- Publisher
- Springer Nature
- DOI
- 10.1007/s00280-007-0631-4
- PMID
- 17989978
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Number of pages
- 10
- Grant note
- CA 16056 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30CA016056 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 08/01/2008
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359870302771
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