Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial) - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Radiotherapy & Oncology Année : 2021

Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial)

Sandrine Dufort
Yannick Crémillieux
Stephen Mcmahon
Daniel Cagney

Résumé

Background and purpose: Brain metastasis impacts greatly on patients & rsquo; quality of life and survival. The phase I NANO-RAD trial assessed the safety and maximum tolerated dose of systemic administration of a novel gadolinium-based nanoparticle, AGuIX, in combination with whole brain radiotherapy in patients with multiple brain metastases not suitable for stereotactic radiotherapy. Materials and methods: Patients with measurable brain metastases received escalating doses of AGuIX nanoparticles (15, 30, 50, 75, or 100 mg/kg intravenously) on the day of initiation of WBRT (30 Gy in 10 fractions) in 5 cohorts of 3 patients each. Toxicity was assessed using NCI Common Terminology Criteria for Adverse Events v4.03. Results: Fifteen patients with 354 metastases were included. No dose-limiting toxic effects were observed up to AGuIX 100 mg/kg. Plasma elimination half-life of AGuIX was similar for all groups (mean 1.3 h; range 0.8 & ndash;3 h). Efficient targeting of metastases (T1 MRI enhancement, tumor selectivity) and persistence of AGuIX contrast enhancement were observed in metastases from patients with primary melanoma, lung, breast, and colon cancers. The concentration of AGuIX in metastases after administration was proportional to the injected dose. Thirteen of 14 evaluable patients had a clinical benefit, with either stabilization or reduction of tumor volume. MRI analysis showed significant correlation between contrast enhancement and tumor response, thus supporting a radiosensitizing effect. Conclusion: Combining AGuIX with radiotherapy for patients with brain metastases is safe and feasible. AGuIX specifically targets brain metastases and is retained within tumors for up to 1 week; ongoing phase II studies will more definitively assess efficacy. (c) 2021 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 160 (2021) 159 & ndash;165 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Fichier principal
Vignette du fichier
PIIS0167814021062198.pdf (1.02 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Licence : CC BY NC ND - Paternité - Pas d'utilisation commerciale - Pas de modification

Dates et versions

hal-03283692 , version 1 (06-09-2021)

Identifiants

Citer

Camille Verry, Sandrine Dufort, Julie Villa, Marylaure Gavard, Carole Iriart, et al.. Theranostic AGuIX nanoparticles as radiosensitizer: A phase I, dose-escalation study in patients with multiple brain metastases (NANO-RAD trial). Radiotherapy & Oncology, 2021, 160, pp.159-165. ⟨10.1016/j.radonc.2021.04.021⟩. ⟨hal-03283692⟩
90 Consultations
69 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More