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Future Oncol. 2017 Apr;13(8):679-693. doi: 10.2217/fon-2016-0357. Epub 2017 Jan 12.

EVESOR, a model-based, multiparameter, Phase I trial to optimize the benefit/toxicity ratio of everolimus and sorafenib.

Author information

1
Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.
2
National Research Centre, Pharmacology Department, Cairo, Egypt.
3
Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Centre Hospitalier Lyon-Sud, Lyon, France.
4
Biochemistry & molecular biology department; Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France.
5
Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
6
Radiology Department, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France.
7
Phase 1 trial Unit, Centre Léon Bérard, Lyon, France.
8
Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
9
Pathology Department, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Lyon, France.

Abstract

AIM:

This novel multiparameter Phase I study aimed to optimize doses/dosing schedules of everolimus and sorafenib drug combination, based on modeling/simulation (NCT01932177).

PATIENTS & METHODS:

About 26 patients with solid tumors were treated in four different dosing schedules. Everolimus once daily + sorafenib twice daily were given continuously in arms A and B, and intermittently in arms C (alternating every other week) and D (everolimus continuous and sorafenib 3 days on/4 days off).

RESULTS:

Continuous schedules exhibited higher toxicity risks than intermittent schedules (64.1 vs 35.9%; p < 0.0001), and trends for lower disease control rates (80 vs 100%). No significant pharmacokinetic interaction was identified.

CONCLUSION:

Feasibility of EVESOR trial is demonstrated. Intermittent schedules might provide better tolerance and efficacy than continuous schedules.

KEYWORDS:

Phase I; administration and dosage; adverse events; angiogenesis inhibitors; everolimus; maximum tolerated dose; modeling; pharmacokinetics; solid tumor; sorafenib; targeted therapy

PMID:
28076966
DOI:
10.2217/fon-2016-0357
[Indexed for MEDLINE]

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