%0 Journal Article
%A Argiles, Guillem
%A Mulet, Nuria
%A Valladares-Ayerbes, Manuel
%A Vieitez, Jose M
%A Gravalos, Cristina
%A Garcia-Alfonso, Pilar
%A Santos, Cristina
%A Tobeña, Maria
%A Garcia-Paredes, Beatriz
%A Benavides, Manuel
%A Cano, María T
%A Loupakis, Fotios
%A Rodriguez-Garrote, Mercedes
%A Rivera, Fernando
%A Goldberg, Richard M
%A Cremolini, Chiara
%A Bennouna, Jaafar
%A Ciardiello, Fortunato
%A Tabernero, Josep M
%A Aranda, Enrique
%T A randomised phase 2 study comparing different dose approaches of induction treatment of regorafenib in previously treated metastatic colorectal cancer patients (REARRANGE trial).
%D 2022
%U http://hdl.handle.net/10668/22181
%X The purpose of this article is to evaluate the safety of two regorafenib dose-escalation approaches in refractory metastatic colorectal cancer (mCRC) patients. Patients with mCRC and progression during or within 3 months following their last standard chemotherapy regimen were randomised to receive the approved dose of regorafenib of 160 mg QD (arm A) or 120 mg QD (arm B) administered as 3 weeks of treatment followed by 1 week off, or 160 mg QD 1 week on/1 week off (arm C). The primary end-point was the percentage of patients with G3/G4 treatment-related adverse events (AEs) in each arm. There were 299 patients randomly assigned to arm A (n = 101), arm B (n = 99), or arm C (n = 99); 297 initiated treatments (arm A n = 100, arm B n = 98, arm C n = 99: population for safety analyses). G3/4 treatment-related AEs occurred in 60%, 55%, and 54% of patients in arms A, B, and C, respectively. The most common G3/4 AEs were hypertension (19, 12, and 20 patients), fatigue (20, 14, and 15 patients), hypokalemia (11, 7, and 10 patients), and hand-foot skin reaction (8, 7, and 3 patients). Median overall survival was 7.4 (IQR 4.0-13.7) months in arm A, 8.6 (IQR 3.8-13.4) in arm B, and 7.1 (IQR 4.4-12.4) in arm C. The alternative regorafenib dosing schedules were feasible and safe in patients with mCRC who had been previously treated with standard therapy. There was a higher numerical improvement on the most clinically relevant AEs in the intermittent dosing arm, particularly during the relevant first two cycles. 
%K Colorectal cancer
%K Drug administration schedule
%K Metastasis
%K Regorafenib
%~