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) 160/120/80/40 122/43/10/43.2/56.8 53.4/46.6 50.6/41.1/1.7/6.3 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 33.5/48.9/17.6 one hundred 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 considerable independent poor prognostic variables (Table 2). HFSR was not extracted as a prognostic element (P = .325). OS curves have been almost certainly separated in accordance with the cumulative dose of regorafenib within the initial two cycles (Figure 1). Median survival occasions of your lower-dose group ( 3180 mg) and higher-dose group ( 3180 mg) were 5.8 and 7.6 months, respectively (P = .045). We also compared the patient characteristics in between the two groups (Table 3). Gender (P = .011) and adjuvant chemotherapy (P = .023) had been statistically skewed in between groups. Even so, they had been not identified as prognostic factors within the multivariate evaluation.Adverse Events Related to RegorafenibWe examined irrespective of whether adverse events caused a reduction in cumulative regorafenib dose. Patients could possibly be separated into two groups determined by the frequency of primary adverse events (Table 4). All grades of skin rash were reported in 7 sufferers (7.7 ) in the higher-dose group and 17 individuals (20 ) inside the lower-dose group. Emergency hospitalization was reported for 5 patients (five.five ) inside the higher-dose group and 16 sufferers (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 significant. Liver dysfunction was not statistically substantial regardless of grade.SIRT2 review Discussionor enrolled in one more clinical trial (n = 1). Consequently, 176 sufferers have been evaluated within this study. Patient characteristics are listed in Table 1. The vast majority of individuals were PS 0 or 1 (91.7 ); pretty much 70 of individuals had a left-sided tumor, and practically half of the individuals had been KRAS wild form. More than 80 of individuals received regorafenib as third- or fourth-line chemotherapy, along with the vast majority of individuals received fluoropyrimidine, irinotecan, oxaliplatin, and bevacizumab. Nearly 70 of sufferers received regorafenib at an initial dose of 160 mg, and also the remaining patients (29.7 ) received a reduced dose. Our multivariate analysis identified total dose till the second cycle 3180 mg, age 65 years, PS 2, hepatic metastasis, and regorafenib initial dose 120 mg as prognostic variables of regorafenib. In groups divided by median dose, regorafenib total dose was associated with OS. It must be noted that a certain cut-off worth for cumulative regorafenib dose was presented since it was not reported STAT6 web previously. Within this study, individuals dropped-out early resulting from adverse events or progressive disease, and we therefore considered the potential for confounding bias. We examined the study population except for early drop-out circumstances in which sufferers discontinued treatment until cycle 2 as a result of serious adverse events or progressive disease in the similar multivariate analysis. In
