EVESOR, a model-based, multiparameter, Phase i trial to optimize the benefit/toxicity ratio of everolimus and sorafenib
© 2017 Future Medicine Ltd. 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.
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 M.M.; Barrois, Catherine; Freyer, Gilles; and You, Benoit, "EVESOR, a model-based, multiparameter, Phase i trial to optimize the benefit/toxicity ratio of everolimus and sorafenib" (2017). Pharmacy. 131.