El-Madani Mévidette, Colomban Olivier, Tod Michel, Maillet Denis, Peron Julien, Rodriguez-Lafrasse Claire, Badary Osama A, Valette Pierre-Jean, Lefort Thibaud, Cassier Philippe, El-Shenawy Siham M, El-Demerdash Ebtehal, Hommel-Fontaine Juliette, Guitton Jerome, Gagnieu Marie-Claude, Ibrahim Bassant Mm, Barrois Catherine, Freyer Gilles, You Benoit
Faculté de Médecine Lyon-Sud, Univ Lyon, Université de Lyon, Université Claude Bernard Lyon 1, EMR UCBL/HCL 3738, Lyon, France.
National Research Centre, Pharmacology Department, Cairo, Egypt.
Future Oncol. 2017 Apr;13(8):679-693. doi: 10.2217/fon-2016-0357. Epub 2017 Jan 12.
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).
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.
Feasibility of EVESOR trial is demonstrated. Intermittent schedules might provide better tolerance and efficacy than continuous schedules.
这项新型多参数I期研究旨在基于建模/模拟优化依维莫司和索拉非尼联合用药的剂量/给药方案（NCT01932177）。
约26例实体瘤患者接受了四种不同给药方案的治疗。A组和B组连续给予依维莫司每日一次+索拉非尼每日两次，C组（每隔一周交替）和D组（依维莫司连续给药，索拉非尼3天给药/4天停药）间歇给药。
连续给药方案的毒性风险高于间歇给药方案（64.1%对35.9%；p<0.0001），且疾病控制率有降低趋势（80%对100%）。未发现明显的药代动力学相互作用。
证实了EVESOR试验的可行性。间歇给药方案可能比连续给药方案具有更好的耐受性和疗效。
