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Eur J Cancer. 2016 Feb;54:120-130. doi: 10.1016/j.ejca.2015.10.013. Epub 2016 Jan 4.

Renal function, body surface area, and age are associated with risk of early-onset fluoropyrimidine-associated toxicity in patients treated with capecitabine-based anticancer regimens in daily clinical care.

Author information

1
Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
2
Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
3
Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
4
Department of Biometrics, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
5
Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands.
6
Division of Gastroenterology and Hepatology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
7
Department of Clinical Pharmacology, Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, The Netherlands. Electronic address: j.schellens@nki.nl.

Abstract

BACKGROUND:

The objective of this analysis was to determine the factors associated with early onset treatment-related toxicity in patients treated with capecitabine-based anticancer regimens in daily clinical care.

PATIENTS AND METHODS:

A total of 1463 patients previously included in a prospective cohort study and treated with standard-of-care capecitabine-based anticancer regimens (monotherapy or combined with other chemotherapy or radiotherapy) were analysed. Logistic regression models were developed to investigate associations between patient- and treatment-related factors and occurrence of early--i.e. cycle one or two--severe (grade ≥ 3) treatment-related toxicity, toxicity-related hospitalisation, and toxicity-related treatment discontinuation. Performance of models was evaluated using receiver-operating characteristic (ROC) curves and internal validity was explored using bootstrap analysis.

RESULTS:

Among 1463 patients included, 231 patients (16%) experienced early severe toxicity, 132 patients (9%) were hospitalised for toxicity, and 146 patients (10%) discontinued treatment for toxicity; in total, 321 patients (22%) experienced any early toxicity-related adverse outcome. Predictors of early grade ≥ 3 toxicity, after adjustment for treatment regimen, were renal function (odds ratio [OR] 0.85 per 10 ml/min/1.73 m(2), p = 0.0007), body surface area (BSA) (OR 0.33 per m(2), p = 0.0053), age (OR 1.14 per decade, p = 0.0891), and elevated pre-treatment uracil concentrations (OR 2.41 per 10 ng/ml, p = 0.0046). Age was significantly associated with fatal treatment-related toxicity (OR 5.75, p = 0.0008). Area under the ROC curve (AUC) of a model to predict early grade ≥ 3 toxicity was 0.704 (95% confidence interval 0.666-0.743, optimism-corrected AUC 0.690).

CONCLUSION:

Renal function, BSA, and age, in addition to pre-treatment uracil, are associated with clinically relevant differences in risk of early severe toxicity in patients treated with capecitabine in routine clinical care.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00838370.

KEYWORDS:

Capecitabine; Fluoropyrimidine-associated toxicity; Safety; Toxicity; adverse events

PMID:
26761784
DOI:
10.1016/j.ejca.2015.10.013
[Indexed for MEDLINE]

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