Prediction of docetaxel toxicity in older cancer patients: a Bayesian network approach.


Journal

Fundamental & clinical pharmacology
ISSN: 1472-8206
Titre abrégé: Fundam Clin Pharmacol
Pays: England
ID NLM: 8710411

Informations de publication

Date de publication:
Dec 2019
Historique:
received: 13 08 2018
revised: 28 03 2019
accepted: 25 04 2019
pubmed: 1 5 2019
medline: 14 4 2020
entrez: 1 5 2019
Statut: ppublish

Résumé

Chemotherapy is an essential therapy in the fight against cancer. Polypathology and polymedication are often encountered in elderly patients, making this population especially at risk for adverse drug reactions, and particularly with cytotoxic drugs. The objective of this study was to build a model to predict high-grade toxicity in elderly patients treated with docetaxel. Data from the trial TAX-108 have been used to create the model. The variable to predict was the occurrence of grade 3 or 4 toxicity. The explanatory variables entered in the model were anthropometric and biological characteristics of patients at inclusion; fragility criteria (SMAF, CIRS-G, performance status); location of the primary tumor; chemotherapy history, radiotherapy or surgery; weekly dose of docetaxel, cumulative dose administered. A Bayesian network model was developed using a global search procedure and an Expectation-Maximization algorithm. A 10-fold cross-validation was performed. A toxicity of grade 3 or higher was observed in 54% of patients. The variables providing the most information were the primary site (19.4%), the dose per course (17.5%), and albuminemia (13.1%). The area under the curve of the model obtained after cross-validation was 74 ± 1.4%. The model built allows classifying correctly 71.21 ± 0.9% of patients in our sample in the cross-validation procedure. The sensitivity and specificity of the model were 75 and 67%, respectively, and the positive and negative predictive values were 73 and 69%. The encouraging results from this first study show that Bayesian networks could help assess the benefit-risk ratio of chemotherapy in elderly patients.

Identifiants

pubmed: 31038767
doi: 10.1111/fcp.12476
doi:

Substances chimiques

Antineoplastic Agents 0
Docetaxel 15H5577CQD

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

679-686

Informations de copyright

© 2019 Société Française de Pharmacologie et de Thérapeutique.

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Auteurs

Fouzy Khayi (F)

Hospices Civils de Lyon, Hôpital Pierre Garraud, 136 rue du commandant Charcot, 69005, Lyon, France.

Laurent Lafarge (L)

Hospices Civils de Lyon, Hôpital Pierre Garraud, 136 rue du commandant Charcot, 69005, Lyon, France.

Catherine Terret (C)

Department of Medical Oncology, Centre Léon Bérard, 28 Prom. Léa et Napoléon Bullukian, 69008, Lyon, France.

Gilles Albrand (G)

Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, 165 Chemin du Grand Revoyet, 69310, Pierre-Bénite, France.

Benoit Falquet (B)

Hospices Civils de Lyon, Hôpital Pierre Garraud, 136 rue du commandant Charcot, 69005, Lyon, France.

Stéphane Culine (S)

Department of Medical Oncology, AP-HP, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010, Paris, France.
Paris-Diderot University, Paris, France.

Sophie Gourgou (S)

Institut du cancer de Montpellier, unité de biométrie, 208, avenue des Apothicaires, 34298, Montpellier, France.
Université de Montpellier, 163, rue Auguste-Broussonnet, 34090, Montpellier, France.

Michel Ducher (M)

Hospices Civils de Lyon, Hôpital Pierre Garraud, 136 rue du commandant Charcot, 69005, Lyon, France.
EMR 3738, Faculté de médecine Lyon-sud, Université Lyon 1, 69310 Pierre-Bénite, Lyon, France.

Laurent Bourguignon (L)

Hospices Civils de Lyon, Hôpital Pierre Garraud, 136 rue du commandant Charcot, 69005, Lyon, France.
UMR CNRS 5558, Laboratoire de Biométrie et Biologie Évolutive, Université Lyon 1, 69100 Villeurbanne, Lyon, France.
ISPB - Faculté de pharmacie, Université Lyon 1, 8 Avenue Rockefeller, 69008, Lyon, France.

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