***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Purpose Fruquintinib ( HMPL-013 ) is a novel oral small molecule compound that selectively inhibits vascular endothelial growth factor receptors-1 , -2 , and -3 with potent inhibitory effects on multiple human tumor xenografts . This first-in-human study was conducted to assess the maximum tolerated dose and dose-limiting toxicities , safety and tolerability , pharmacokinetics , and preliminary anti-tumor activity of fruquintinib . Methods Patients 18–70 years old with advanced solid tumors refractory to st and ard therapies were recruited .  Fruquintinib was administered orally in 4-week repeating cycles in two regimens , either once daily continuously or once daily for 3-week on/1-week off , until discontinuation due to toxicity or tumor progression . Adverse events were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0.3 . Pharmacokinetic parameters were measured after a single dose and in multiple dosing . Tumor response was assessed by Response Evaluation Criteria in Solid Tumors v1.0 . Results Forty patients were enrolled into 5 cohorts in continuous regimen and 2 cohorts in 3-week-on/1-week-off regimen . The most common grade 3/4 adverse events were h and –foot skin reaction , hypertension , and thrombocytopenia . PK analysis showed good and rapid absorption followed by slow terminal elimination with a mean half-life of approximately 42 h which was consistent across all dose groups . Thirty-four patients were evaluable for  tumor response  , including 14 with partial response and 14 with stable disease . Conclusions Fruquintinib showed an acceptable safety profile and preliminary evidence of anti-tumor activity in patients with advanced solid tumors . The recommended dose was determined to be either 4 mg QD on a continuous regimen or 5 mg QD on a 3-week-on/1-week-off regimen Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Abstract Objective To describe the use of regorafenib for the treatment of metastatic colorectal cancer ( mCRC ) in clinical practice in the Czech Republic , and to describe the clinical outcomes of patients in terms of safety and survival . Patients and Methods The data of patients treated with regorafenib were extracted from the national CORECT registry . The CORECT registry is a non-interventional post-marketing data base , gathering information about patients with CRC and treated with targeted agents . Twenty oncology centres in the Czech Republic contributed to this registry . Collected data included patients ’ characteristics , disease history , cancer treatments , response to treatments and safety . Results A total of 148 patients treated with regorafenib in clinical practice were analysed . At regorafenib initiation , almost all patients were fully active or slightly restricted in physical activity .  Regorafenib was not administered as first-line treatment in any patient . Median progression-free survival was 3.5 months and median overall survival was 9.3 months . One-year survival rate was 44.6 % . Four partial responses were observed and 51 stable diseases . Progression was observed in 66 patients ( 44.6 % ) . The main reported adverse events were skin toxicity ( 5.4 % ) and fatigue ( 2.0 % ) . Conclusions Regorafenib is a well-established treatment for pretreated patients with mCRC , however real-life data are scarce . Our results demonstrated slightly better efficacy of regorafenib and better safety profile in patients with mCRC compared to the r and omised trials The FDA approved TAS-102 ( Lonsurf ; Taiho Oncology , Inc. ) for the treatment of patients with metastatic colorectal cancer ( mCRC ) who have been previously treated with fluoropyrimidine- , oxaliplatin- , and irinotecan-based chemotherapy ; an anti-VEGF biological therapy ; and if RAS wild type , an anti-EGFR therapy . In an international , multicenter , double-blinded , placebo-controlled trial ( TPU-TAS-102 - 301 , herein referred to as RECOURSE ) , 800 patients with previously treated mCRC were r and omly allocated ( 2:1 ) to receive either TAS-102 35 mg/m2 orally twice daily after meals on days 1 through 5 and 8 through 12 of each 28-day cycle ( n = 534 ) or matching placebo ( n = 266 ) . The trial demonstrated a statistically significant improvement in overall survival for those r and omized to receive TAS-102 , with a median survival of 7.1 months in the TAS-102 arm [ confidence interval ( CI ) , 6.5–7.8 ] and 5.3 months in the placebo arm [ CI , 4.6–6.0 ; hazard ratio ( HR ) , 0.68 ; 95 % CI , 0.58–0.81 ; P < 0.001 , stratified log-rank test ] . The trial also demonstrated a statistically significant prolongation of progression-free survival ( HR , 0.47 ; 95 % CI , 0.40–0.55 ; P < 0.001 ) . The most common adverse reactions , in order of decreasing frequency , observed in the patients who received TAS-102 were anemia , neutropenia , asthenia/fatigue , nausea , thrombocytopenia , decreased appetite , diarrhea , vomiting , abdominal pain , and pyrexia . Adverse events led to discontinuation of TAS-102 in 3.6 % of patients , and 13.7 % required a dose reduction . The most common adverse reactions leading to dose reduction were neutropenia , anemia , febrile neutropenia , fatigue , and diarrhea . Clin Cancer Res ; 23(12 ) ; 2924–7 . © 2017 AACR 
    Output:
    
Based on efficacy and safety , there was a tendency that fruquintinib was superior to regorafenib , as a whole , regorafenib and fruquintinib demonstrated similar clinical benefit for patients with refractory mCRC .
It seems that fruquintinib has less toxic in all- grade toxicity when compared with regorafenib