Cargando…

A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials

BACKGROUND: The incidence and clinical significance of electrolyte abnormalities (EAs) in phase I clinical trials are unknown. The objective of this study is to evaluate the incidence and severity of EAs, graded according to CTCAE, v4.03, to identify variables associated with EAs and their prognosti...

Descripción completa

Detalles Bibliográficos
Autores principales: Ingles Garces, Alvaro H., Ang, Joo Ern, Ameratunga, Malaka, Chénard-Poirier, Maxime, Dolling, David, Diamantis, Nikolaos, Seeramreddi, Satyanarayana, Sundar, Raghav, de Bono, Johann, Lopez, Juanita, Banerji, Udai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259582/
https://www.ncbi.nlm.nih.gov/pubmed/30316017
http://dx.doi.org/10.1016/j.ejca.2018.08.019
_version_ 1783374711551426560
author Ingles Garces, Alvaro H.
Ang, Joo Ern
Ameratunga, Malaka
Chénard-Poirier, Maxime
Dolling, David
Diamantis, Nikolaos
Seeramreddi, Satyanarayana
Sundar, Raghav
de Bono, Johann
Lopez, Juanita
Banerji, Udai
author_facet Ingles Garces, Alvaro H.
Ang, Joo Ern
Ameratunga, Malaka
Chénard-Poirier, Maxime
Dolling, David
Diamantis, Nikolaos
Seeramreddi, Satyanarayana
Sundar, Raghav
de Bono, Johann
Lopez, Juanita
Banerji, Udai
author_sort Ingles Garces, Alvaro H.
collection PubMed
description BACKGROUND: The incidence and clinical significance of electrolyte abnormalities (EAs) in phase I clinical trials are unknown. The objective of this study is to evaluate the incidence and severity of EAs, graded according to CTCAE, v4.03, to identify variables associated with EAs and their prognostic significance in a phase I population. METHODS: A retrospective chart review was performed of 1088 cases in 82 phase I clinical trials consecutively treated from 2011 to 2015 at the Drug Development Unit of the Royal Marsden Hospital. Cox regression analysis was performed to examine the relationship between overall survival (OS) and baseline characteristics, treating the occurrence of grade III/IV EAs as a time-varying covariate. RESULTS: The most common emergent EAs (all grades) were as follows: hyponatraemia 62%, hypokalaemia 40%, hypophosphataemia 32%, hypomagnesaemia 17% and hypocalcaemia 12%. Grade III/IV EAs occurred in 19% of cases. Grade III/IV EAs occurred during the dose-limiting toxicity window in 8.46% of cases. Diarrhoea was associated with hypomagnesaemia at all grades (p < 0.001), hyponatraemia at all grades (p = 0.006) and with G3/G4 hypokalaemia (p = 0.02). Baseline hypoalbuminaemia and hyponatraemia were associated with a higher risk of developing other EAs during the trial in the univariate analysis. Patients who developed grade III/IV EAs during follow-up had an inferior median OS (26 weeks vs 37 weeks, hazard ratio = 1.61; p < 0.001). CONCLUSION: This is the first study to demonstrate the clinical significance of baseline hypoalbuminaemia and hyponatraemia, which are predictors of development of other EAs in phase I patients. Grade III/IV EAs are adverse prognostic factors of OS independent of serum albumin levels.
format Online
Article
Text
id pubmed-6259582
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Elsevier Science Ltd
record_format MEDLINE/PubMed
spelling pubmed-62595822018-12-06 A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials Ingles Garces, Alvaro H. Ang, Joo Ern Ameratunga, Malaka Chénard-Poirier, Maxime Dolling, David Diamantis, Nikolaos Seeramreddi, Satyanarayana Sundar, Raghav de Bono, Johann Lopez, Juanita Banerji, Udai Eur J Cancer Article BACKGROUND: The incidence and clinical significance of electrolyte abnormalities (EAs) in phase I clinical trials are unknown. The objective of this study is to evaluate the incidence and severity of EAs, graded according to CTCAE, v4.03, to identify variables associated with EAs and their prognostic significance in a phase I population. METHODS: A retrospective chart review was performed of 1088 cases in 82 phase I clinical trials consecutively treated from 2011 to 2015 at the Drug Development Unit of the Royal Marsden Hospital. Cox regression analysis was performed to examine the relationship between overall survival (OS) and baseline characteristics, treating the occurrence of grade III/IV EAs as a time-varying covariate. RESULTS: The most common emergent EAs (all grades) were as follows: hyponatraemia 62%, hypokalaemia 40%, hypophosphataemia 32%, hypomagnesaemia 17% and hypocalcaemia 12%. Grade III/IV EAs occurred in 19% of cases. Grade III/IV EAs occurred during the dose-limiting toxicity window in 8.46% of cases. Diarrhoea was associated with hypomagnesaemia at all grades (p < 0.001), hyponatraemia at all grades (p = 0.006) and with G3/G4 hypokalaemia (p = 0.02). Baseline hypoalbuminaemia and hyponatraemia were associated with a higher risk of developing other EAs during the trial in the univariate analysis. Patients who developed grade III/IV EAs during follow-up had an inferior median OS (26 weeks vs 37 weeks, hazard ratio = 1.61; p < 0.001). CONCLUSION: This is the first study to demonstrate the clinical significance of baseline hypoalbuminaemia and hyponatraemia, which are predictors of development of other EAs in phase I patients. Grade III/IV EAs are adverse prognostic factors of OS independent of serum albumin levels. Elsevier Science Ltd 2018-11 /pmc/articles/PMC6259582/ /pubmed/30316017 http://dx.doi.org/10.1016/j.ejca.2018.08.019 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ingles Garces, Alvaro H.
Ang, Joo Ern
Ameratunga, Malaka
Chénard-Poirier, Maxime
Dolling, David
Diamantis, Nikolaos
Seeramreddi, Satyanarayana
Sundar, Raghav
de Bono, Johann
Lopez, Juanita
Banerji, Udai
A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials
title A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials
title_full A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials
title_fullStr A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials
title_full_unstemmed A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials
title_short A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials
title_sort study of 1088 consecutive cases of electrolyte abnormalities in oncology phase i trials
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259582/
https://www.ncbi.nlm.nih.gov/pubmed/30316017
http://dx.doi.org/10.1016/j.ejca.2018.08.019
work_keys_str_mv AT inglesgarcesalvaroh astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT angjooern astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT ameratungamalaka astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT chenardpoiriermaxime astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT dollingdavid astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT diamantisnikolaos astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT seeramreddisatyanarayana astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT sundarraghav astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT debonojohann astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT lopezjuanita astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT banerjiudai astudyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT inglesgarcesalvaroh studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT angjooern studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT ameratungamalaka studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT chenardpoiriermaxime studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT dollingdavid studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT diamantisnikolaos studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT seeramreddisatyanarayana studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT sundarraghav studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT debonojohann studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT lopezjuanita studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials
AT banerjiudai studyof1088consecutivecasesofelectrolyteabnormalitiesinoncologyphaseitrials