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 five.1 two.2 29.5/70.five 69.3/30.7 47.1/52.3/0.six 58.5/41.five 31.3/67/60.2 33.5/48.9/17.6 100 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) had been extracted as statistically significant independent poor prognostic elements (Table two). HFSR was not extracted as a prognostic factor (P = .325). OS curves were possibly separated in accordance with the mGluR6 Purity & Documentation cumulative dose of regorafenib within the initial 2 cycles (Figure 1). Median survival instances of your lower-dose group ( 3180 mg) and higher-dose group ( 3180 mg) had been five.eight and 7.6 months, respectively (P = .045). We also compared the patient qualities in between the two groups (Table 3). Gender (P = .011) and adjuvant chemotherapy (P = .023) had been statistically skewed between groups. Nonetheless, they were not identified as prognostic variables in the multivariate evaluation.Adverse Events Associated to RegorafenibWe examined no matter whether adverse events triggered a reduction in cumulative regorafenib dose. Individuals may very well be separated into 2 groups according to the frequency of principal adverse events (Table four). All grades of skin rash have been reported in 7 patients (7.7 ) in the higher-dose group and 17 sufferers (20 ) inside the lower-dose group. Emergency hospitalization was reported for 5 individuals (five.5 ) inside the higher-dose group and 16 individuals (18.8 ) within the lower-dose group. All grades of HFSR (P = .01), grade 3 hypertension (P = .008), all grades (P = .017) and grade 3 (P = .018) skin rash, and emergency hospitalization (P = .006) were statistically substantial. Liver dysfunction was not statistically substantial irrespective of grade.Discussionor enrolled in an additional clinical trial (n = 1). Consequently, 176 patients had been evaluated in this study. Patient traits are listed in Table 1. The vast majority of patients have been PS 0 or 1 (91.7 ); nearly 70 of sufferers had a left-sided tumor, and pretty much half in the patients had been KRAS wild sort. Much 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. Virtually 70 of patients received regorafenib at an initial dose of 160 mg, and the remaining sufferers (29.7 ) received a decrease 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 needs to be noted that a certain cut-off value for cumulative regorafenib dose was presented because it was not reported previously. In this study, individuals dropped-out early on RGS4 Species account of adverse events or progressive disease, and we thus thought of the potential for confounding bias. We examined the study population except for early drop-out situations in which patients discontinued therapy till cycle two as a result of severe adverse events or progressive illness in the very same multivariate analysis. In