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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
Effects of selenomethionine on acute toxicities from concurrent chemoradiation for inoperable stage III non-small cell lung cancer
Michael Mix, Nithya Ramnath, Jorge Gomez, Charles de Groot, Saju Rajan, Shiva Dibaj, Wei Tan, Youcef Rustum, Michael B Jameson, Anurag K Singh
Michael Mix, Jorge Gomez, Saju Rajan, Anurag K Singh, Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, United States
Nithya Ramnath, Department of Medical Oncology, University of Michigan, Ann Arbor, MI 48109, United States
Charles de Groot, Department of Radiation Oncology, Regional Cancer Centre, Waikato Hospital, Hamilton West 3204, New Zealand
Shiva Dibaj, Wei Tan, Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY 14263, United States
Youcef Rustum, Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, NY 14263, United States
Michael B Jameson, Department of Oncology, Regional Cancer Centre, Waikato Hospital, Hamilton West 3204, New Zealand
Author contributions: Mix M drafted the manuscript, and assisted with data analysis; Ramnath N participated in design and oversight of the study, and was involved with data collection; Gomez J participated in design of the study, and was involved with data collection; de Groot C was involved with data collection, and assisted with data analysis; Rajan S drafted the manuscript, and assisted with data analysis; Dibaj S participated in study design and performed statistical analysis; Tan W participated in study design and performed statistical analysis; Rustum Y participated in design of the study, and carried out selenium analyses; Jameson MB participated in design of the study, was involved with data collection, and carried out selenium analyses; Singh AK drafted the manuscript, and assisted with data analysis; all authors read and approved the final manuscript.
Supported by The Health Research Council of New Zealand.
Institutional review board statement: The study was reviewed and approved by the institutional review boards of Roswell Park Cancer Institute (Buffalo, NY, USA) and the Northern Y Regional Ethics Committee in New Zealand.
Clinical trial registration statement: The clinical trial is registered with ClinicalTrials.gov, using identifier NCT00526890. Details can be found at https://clinicaltrials.gov/ct2/show/NCT00526890?term=NCT00526890&rank=1.
Informed consent statement: All study participants, or their legal guardian, provided written consent prior to study enrollment.
Conflict-of-interest statement: The authors of this manuscript having no conflicts of interest to disclose.
Data sharing statement: There is no additional data available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Anurag K Singh, MD, Professor, Director, Department of Radiation Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, United States.
anurag.singh@roswellpark.org
Telephone: +1-716-8451180 Fax: +1-716-8457616
Received: March 12, 2015
Peer-review started: March 12, 2015
First decision: May 13, 2015
Revised: June 6, 2015
Accepted: June 18, 2015
Article in press: June 19, 2015
Published online: October 10, 2015
Processing time: 215 Days and 7.6 Hours
AIM: To prospectively determine the safety and tolerability of oral L-selenomethionine (SLM) with concurrent chemoradiation (CCRT) for Stage III non-small cell lung cancer (NSCLC) and estimate if the incidence and/or severity of adverse events could be reduced by its use.
METHODS: Sixteen patients with stage III NSCLC were accrued to this single arm, phase II study. CCRT consisted of radiation given at 2 Gy per fraction for 30-33 fractions, 5 d per week with concurrent weekly IV paclitaxel 50 mg/m2 followed by carboplatin dosed at an area under the time-concentration curve of 2. SLM was dosed in a loading phase at 4800 μg twice daily for one week prior to CCRT followed by once daily dosing during treatment.
RESULTS: No selenium-related toxicity was observed. Analysis revealed grade 3 or higher esophagitis in 3 of 16 patients (19%), pneumonitis in 0, leukopenia in 2 (12.5%), and anemia in 1 (6%); the latter two were significantly reduced when compared to the protocol-stated expected rate of 35% (P = 0.045 for leukopenia, and P < 0.01 for anemia). Median overall survival was 14.9 mo and median failure-free survival was 9 mo (95%CI: 3.3-21.5).
CONCLUSION: There may be some protective benefit of selenium in the setting of CCRT for inoperable NSCLC. The data suggests decreased rates of myelosuppression when compared to similarly-treated historical and contemporary controls. Further evaluation of selenium in this setting may be warranted.
Core tip: This was a prospective international phase II trial with 16 patients seeking to evaluate the effect of selenomethionine on acute toxicity in the setting of concurrent chemoradiaiton for locally advanced, inoperable non-small cell lung cancer. Selenium proved to be well tolerated and led to significantly reduced rates of myelosuppression.
