Cargando…

Long-term relationship between everolimus blood concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma: a prospective study

BACKGROUND: Everolimus is an oral inhibitor of mammalian target of rapamycin, approved for metastatic renal cell carcinoma (mRCC). Recently, personalized medicine through therapeutic drug monitoring (TDM) is recommended in cancer therapy. In this study, the relationship between everolimus blood conc...

Descripción completa

Detalles Bibliográficos
Autores principales: Takasaki, Shinya, Yamaguchi, Hiroaki, Kawasaki, Yoshihide, Kikuchi, Masafumi, Tanaka, Masaki, Ito, Akihiro, Mano, Nariyasu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413453/
https://www.ncbi.nlm.nih.gov/pubmed/30906563
http://dx.doi.org/10.1186/s40780-019-0135-5
_version_ 1783402823748157440
author Takasaki, Shinya
Yamaguchi, Hiroaki
Kawasaki, Yoshihide
Kikuchi, Masafumi
Tanaka, Masaki
Ito, Akihiro
Mano, Nariyasu
author_facet Takasaki, Shinya
Yamaguchi, Hiroaki
Kawasaki, Yoshihide
Kikuchi, Masafumi
Tanaka, Masaki
Ito, Akihiro
Mano, Nariyasu
author_sort Takasaki, Shinya
collection PubMed
description BACKGROUND: Everolimus is an oral inhibitor of mammalian target of rapamycin, approved for metastatic renal cell carcinoma (mRCC). Recently, personalized medicine through therapeutic drug monitoring (TDM) is recommended in cancer therapy. In this study, the relationship between everolimus blood concentration and clinical outcomes on a long-term were evaluated in Japanese patients with mRCC. METHODS: Patients with mRCC were enrolled following treatment with everolimus at Tohoku University Hospital between April 2012 and December 2016. The relationship between everolimus trough blood concentration on day 8 of everolimus therapy and just before discontinuation or dose reduction, and their adverse events were evaluated. Patients were divided into two groups based on the median of everolimus blood concentration on day 8 of treatment, and the profiles of adverse events, and efficacy [time to treatment failure (TTF) and progression-free survival (PFS)] were evaluated. RESULTS: The median (range) everolimus blood concentrations on day 8 after starting everolimus administration and just before discontinuation or dose reduction were 15.3 (8.1–28.0) ng/mL and 14.8 (6.4–58.4) ng/mL, respectively, with no significant difference between these values (P = 0.3594). Patients (n = 6) with discontinuation or dose reduction following adverse events in everolimus therapy had significantly higher blood concentrations than patients (n = 4) with dose maintenance on both day 8 (median, 18.0 vs 8.2 ng/mL; P = 0.0139) and just before discontinuation or dose reduction (median, 22.9 vs 9.7 ng/mL; P = 0.0142). Median TTF and PFS of the total patients (n = 10) were 96 days (95% confidence interval [CI], 26–288) and 235 days (95% CI, 28–291), respectively. Subgroup analysis showed that TTF of the patients with > 15.3 ng/mL (n = 5) was not significantly different from that of the patients with ≤15.3 ng/mL (n = 5; P = 0.5622). Similarly, PFS of the patients with > 15.3 ng/mL was not significantly different from that of the patients with ≤15.3 ng/mL (P = 0.3436). CONCLUSIONS: This study demonstrated the long-term relationship between everolimus blood level and clinical outcomes and adverse events in Japanese patients with mRCC. Thus, TDM in everolimus therapy could be a useful tool for the early prediction of adverse events for Japanese patients with mRCC.
format Online
Article
Text
id pubmed-6413453
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-64134532019-03-22 Long-term relationship between everolimus blood concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma: a prospective study Takasaki, Shinya Yamaguchi, Hiroaki Kawasaki, Yoshihide Kikuchi, Masafumi Tanaka, Masaki Ito, Akihiro Mano, Nariyasu J Pharm Health Care Sci Research Article BACKGROUND: Everolimus is an oral inhibitor of mammalian target of rapamycin, approved for metastatic renal cell carcinoma (mRCC). Recently, personalized medicine through therapeutic drug monitoring (TDM) is recommended in cancer therapy. In this study, the relationship between everolimus blood concentration and clinical outcomes on a long-term were evaluated in Japanese patients with mRCC. METHODS: Patients with mRCC were enrolled following treatment with everolimus at Tohoku University Hospital between April 2012 and December 2016. The relationship between everolimus trough blood concentration on day 8 of everolimus therapy and just before discontinuation or dose reduction, and their adverse events were evaluated. Patients were divided into two groups based on the median of everolimus blood concentration on day 8 of treatment, and the profiles of adverse events, and efficacy [time to treatment failure (TTF) and progression-free survival (PFS)] were evaluated. RESULTS: The median (range) everolimus blood concentrations on day 8 after starting everolimus administration and just before discontinuation or dose reduction were 15.3 (8.1–28.0) ng/mL and 14.8 (6.4–58.4) ng/mL, respectively, with no significant difference between these values (P = 0.3594). Patients (n = 6) with discontinuation or dose reduction following adverse events in everolimus therapy had significantly higher blood concentrations than patients (n = 4) with dose maintenance on both day 8 (median, 18.0 vs 8.2 ng/mL; P = 0.0139) and just before discontinuation or dose reduction (median, 22.9 vs 9.7 ng/mL; P = 0.0142). Median TTF and PFS of the total patients (n = 10) were 96 days (95% confidence interval [CI], 26–288) and 235 days (95% CI, 28–291), respectively. Subgroup analysis showed that TTF of the patients with > 15.3 ng/mL (n = 5) was not significantly different from that of the patients with ≤15.3 ng/mL (n = 5; P = 0.5622). Similarly, PFS of the patients with > 15.3 ng/mL was not significantly different from that of the patients with ≤15.3 ng/mL (P = 0.3436). CONCLUSIONS: This study demonstrated the long-term relationship between everolimus blood level and clinical outcomes and adverse events in Japanese patients with mRCC. Thus, TDM in everolimus therapy could be a useful tool for the early prediction of adverse events for Japanese patients with mRCC. BioMed Central 2019-03-12 /pmc/articles/PMC6413453/ /pubmed/30906563 http://dx.doi.org/10.1186/s40780-019-0135-5 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Takasaki, Shinya
Yamaguchi, Hiroaki
Kawasaki, Yoshihide
Kikuchi, Masafumi
Tanaka, Masaki
Ito, Akihiro
Mano, Nariyasu
Long-term relationship between everolimus blood concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma: a prospective study
title Long-term relationship between everolimus blood concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma: a prospective study
title_full Long-term relationship between everolimus blood concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma: a prospective study
title_fullStr Long-term relationship between everolimus blood concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma: a prospective study
title_full_unstemmed Long-term relationship between everolimus blood concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma: a prospective study
title_short Long-term relationship between everolimus blood concentration and clinical outcomes in Japanese patients with metastatic renal cell carcinoma: a prospective study
title_sort long-term relationship between everolimus blood concentration and clinical outcomes in japanese patients with metastatic renal cell carcinoma: a prospective study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413453/
https://www.ncbi.nlm.nih.gov/pubmed/30906563
http://dx.doi.org/10.1186/s40780-019-0135-5
work_keys_str_mv AT takasakishinya longtermrelationshipbetweeneverolimusbloodconcentrationandclinicaloutcomesinjapanesepatientswithmetastaticrenalcellcarcinomaaprospectivestudy
AT yamaguchihiroaki longtermrelationshipbetweeneverolimusbloodconcentrationandclinicaloutcomesinjapanesepatientswithmetastaticrenalcellcarcinomaaprospectivestudy
AT kawasakiyoshihide longtermrelationshipbetweeneverolimusbloodconcentrationandclinicaloutcomesinjapanesepatientswithmetastaticrenalcellcarcinomaaprospectivestudy
AT kikuchimasafumi longtermrelationshipbetweeneverolimusbloodconcentrationandclinicaloutcomesinjapanesepatientswithmetastaticrenalcellcarcinomaaprospectivestudy
AT tanakamasaki longtermrelationshipbetweeneverolimusbloodconcentrationandclinicaloutcomesinjapanesepatientswithmetastaticrenalcellcarcinomaaprospectivestudy
AT itoakihiro longtermrelationshipbetweeneverolimusbloodconcentrationandclinicaloutcomesinjapanesepatientswithmetastaticrenalcellcarcinomaaprospectivestudy
AT manonariyasu longtermrelationshipbetweeneverolimusbloodconcentrationandclinicaloutcomesinjapanesepatientswithmetastaticrenalcellcarcinomaaprospectivestudy