118/106 Number of prior chemotherapies 2/3/4 59/86/31 Prior chemotherapy Fluoropyrimidine 176 Irinotecan 174 Oxaliplatin 175 Bevacizumab 163 Anti-EGFR 79 Regorafenib initial dose (mg) 160/120/80/40 122/43/10/43.2/56.eight 53.4/46.6 50.6/41.1/1.7/6.three 59.7 33 5.1 two.2 29.5/70.5 69.3/30.7 47.1/52.3/0.6 58.5/41.5 31.3/67/60.2 33.5/48.9/17.six 100 98.9 99.4 92.six 44.9 69.3/24.4/5.7/0.second cycle 3180 mg (HR 1.71, 95 CI, 1.20.44, P = .003), age 65 years (HR 1.96, 95 CI, 1.36.86, P .001), PS two (HR 1.81, 95 CI, 1.28.57, P = .001), hepatic metastasis (HR two.86, 95 CI, 1.90.30, P .001), and regorafenib initial dose 120 mg (HR 1.71, 95 CI, 1.14.58, P = .01) were extracted as statistically Nav1.2 MedChemExpress substantial independent poor prognostic variables (Table two). HFSR was not extracted as a prognostic element (P = .325). OS curves were probably separated in line with the cumulative dose of regorafenib inside the initial 2 cycles (Figure 1). Median survival occasions with the lower-dose group ( 3180 mg) and higher-dose group ( 3180 mg) have been five.8 and 7.6 months, respectively (P = .045). We also compared the patient characteristics in between the 2 groups (Table 3). Gender (P = .011) and adjuvant chemotherapy (P = .023) were statistically skewed in between groups. Even so, they were not identified as prognostic factors within the multivariate analysis.Adverse Events Related to RegorafenibWe examined whether adverse events brought on a reduction in cumulative regorafenib dose. Patients may be separated into two groups according to the frequency of primary adverse events (Table four). All grades of skin rash had been reported in 7 patients (7.7 ) within the higher-dose group and 17 sufferers (20 ) within the lower-dose group. NK1 Molecular Weight Emergency hospitalization was reported for 5 patients (5.five ) inside the higher-dose group and 16 patients (18.eight ) inside the lower-dose group. All grades of HFSR (P = .01), grade three hypertension (P = .008), all grades (P = .017) and grade 3 (P = .018) skin rash, and emergency hospitalization (P = .006) had been statistically considerable. Liver dysfunction was not statistically substantial regardless of grade.Discussionor enrolled in an additional clinical trial (n = 1). Consequently, 176 individuals had been evaluated within this study. Patient traits are listed in Table 1. The vast majority of sufferers have been PS 0 or 1 (91.7 ); pretty much 70 of patients had a left-sided tumor, and virtually half in the sufferers have been KRAS wild type. A lot more than 80 of patients received regorafenib as third- or fourth-line chemotherapy, along with the vast majority of patients received fluoropyrimidine, irinotecan, oxaliplatin, and bevacizumab. Practically 70 of sufferers received regorafenib at an initial dose of 160 mg, and the remaining patients (29.7 ) received a lower dose. Our multivariate evaluation identified total dose till the second cycle 3180 mg, age 65 years, PS two, hepatic metastasis, and regorafenib initial dose 120 mg as prognostic variables of regorafenib. In groups divided by median dose, regorafenib total dose was connected with OS. It needs to be noted that a particular cut-off value for cumulative regorafenib dose was presented since it was not reported previously. In this study, patients dropped-out early on account of adverse events or progressive illness, and we for that reason deemed the prospective for confounding bias. We examined the study population except for early drop-out circumstances in which patients discontinued remedy till cycle 2 as a result of extreme adverse events or progressive illness inside the similar multivariate evaluation. In
