Optimal design for informative protocols in xenograft tumor growth inhibition experiments in mice

Abstract : Tumor growth inhibition (TGI) models are increasingly used during preclinical drug development in oncology for the in vivo evaluation of antitumor effect. Tumor sizes are measured in xenografted mice, often only during and shortly after treatment, thus preventing correct identification of some TGI model parameters. Our aims were i) to evaluate the importance of including measurements during tumor regrowth; ii) to investigate the proportions of mice included in each arm. For these purposes, optimal design theory based on the Fisher information matrix implemented in PFIM4.0 was applied. Published xenograft experiments, involving different drugs, schedules and cell lines, were used to help optimize experimental settings and parameters using the Simeoni TGI model. For each experiment, a two-arm design, i.e. control vs treatment, was optimized with or without the constraint of not sampling during tumor regrowth, i.e. " short " and " long " studies, respectively. In long studies, measurements could be taken up to 6 grams of tumor weight, whereas in short studies the experiment was stopped three days after the end of treatment. Predicted relative standard errors were smaller in long studies than in corresponding short studies. Some optimal measurement times were located in the regrowth phase, highlighting the importance of continuing the experiment after the end of treatment. In the four-arm designs, the results showed that the proportions of control and treated mice can differ. To conclude, making measurements during tumor regrowth should become a general rule for informative preclinical studies in oncology, especially when a delayed drug effect is suspected.
Type de document :
Article dans une revue
AAPS Journal, American Association of Pharmaceutical Scientists, 2016, 18 ((5)), pp.1233-43. 〈10.1208/s12248-016-9924-z〉
Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-01374085
Contributeur : Thu Thuy Nguyen <>
Soumis le : jeudi 29 septembre 2016 - 16:47:59
Dernière modification le : lundi 4 décembre 2017 - 10:36:47
Document(s) archivé(s) le : vendredi 30 décembre 2016 - 14:22:06

Fichiers

Manuscript_Lestini_HalInserm.p...
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

Citation

Giulia Lestini, France Mentré, Paolo Magni. Optimal design for informative protocols in xenograft tumor growth inhibition experiments in mice. AAPS Journal, American Association of Pharmaceutical Scientists, 2016, 18 ((5)), pp.1233-43. 〈10.1208/s12248-016-9924-z〉. 〈inserm-01374085〉

Partager

Métriques

Consultations de la notice

140

Téléchargements de fichiers

34