A study of 1088 consecutive cases of electrolyte abnormalities in oncology phase I trials.
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Date
2018-11-01Author
Ingles Garces, AH
Ang, JE
Ameratunga, M
Chénard-Poirier, M
Dolling, D
Diamantis, N
Seeramreddi, S
Sundar, R
de Bono, J
Lopez, J
Banerji, U
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Humans
Neoplasms
Hypertension
Water-Electrolyte Imbalance
Diarrhea
Antineoplastic Agents
Prognosis
Incidence
Proportional Hazards Models
Retrospective Studies
Comorbidity
London
Female
Male
Clinical Trials, Phase I as Topic
Kaplan-Meier Estimate
Molecular Targeted Therapy
Research team
Medicine (de Bono Prostate)
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Language
eng
Date accepted
2018-08-28
License start date
2018-11
Citation
European journal of cancer (Oxford, England : 1990), 2018, 104 pp. 32 - 38
Publisher
ELSEVIER SCI LTD