***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: Background : TAS-102 consists of α , α , α-trifluorothymidine ( TFT ) and an inhibitor of thymidine phosphorylase ( TPI ) . We conducted a dose-escalation phase I study in Japanese patients with advanced solid tumours . Methods : TAS-102 was administered twice daily on days 1–5 and days 8–12 in a 28-day cycle to patients with solid tumours refractory to st and ard chemotherapy  , to determine its maximum tolerated dose ( MTD ) , dose-limiting toxicities ( DLTs ) , and pharmacokinetics ( PKs ) . MTD was evaluated in cycle 1 . Results : Safety and PKs were evaluated in 21 patients treated with TAS-102  at 30 , 40 , 50 , 60 , or 70 mg m−2 per day . DLTs , such as grade 4 leucopenia , grade 4 neutropenia , and grade 4 thrombocytopenia , were observed in two patients at doses of 30 and 70 mg m−2 . α , α , α-trifluorothymidine and TPI exposures increased dose dependently , and the percentage of decrease in neutrophil count and TFT exposure were significantly correlated . The disease control rate was 50.0 % with a median progression-free survival of 2.4 months in 18 colorectal cancer patients . The dose of TAS-102 was not increased above 70 mg m−2 per day because of the increased tendency for grade 3 and 4 neutropenia , and 70 mg m−2 per day was the recommended dose for phase II studies . Conclusions : TAS-102 at 70 mg m−2 per day was tolerated in Japanese patients with advanced solid tumours . Phase II studies are ongoing in patients with colorectal cancer Background : In a phase I dose-escalation study , regorafenib demonstrated tolerability and antitumour activity in solid tumour patients . The study was exp and ed to focus on patients with metastatic colorectal cancer ( CRC ) . Methods : Patients received oral regorafenib 60–220 mg daily ( 160 mg daily in the extension cohort ) in cycles of 21 days on , 7 days off treatment . Assessment s included toxicity , response , pharmacokinetics and pharmacodynamics . Results : Thirty-eight patients with heavily pretreated CRC ( median 4 prior lines of therapy , range 0–7 ) were enrolled in the dose-escalation and extension phases ; 26 patients received regorafenib 160 mg daily . Median treatment duration was 53 days ( range 7–280 days ) . The most common treatment-related toxicities included h and –foot skin reaction , fatigue , voice change and rash .  Twenty-seven patients were evaluable for response : 1 achieved partial response and 19 had stable disease . Median progression-free survival was 107 days ( 95 % CI , 66–161 ) . At steady state , regorafenib and its active metabolites had similar systemic exposure . Pharmacodynamic assessment indicated decreased tumour perfusion in most patients . Conclusion : Regorafenib showed tolerability and antitumour activity in patients with metastatic CRC . This exp and ed-cohort phase I study provided the foundation for further clinical trials of regorafenib in this patient population Purpose : Regorafenib is a novel oral multikinase inhibitor of angiogenic ( VEGFR1 - 3 , TIE2 ) , stromal ( PDGFR-β , FGFR ) , and oncogenic kinases ( KIT , RET , and RAF ) . This first-in-man , phase I dose – escalation study assessed the safety , pharmacokinetic , pharmacodynamic , and efficacy profiles of regorafenib in patients with advanced solid tumors . Patients and Methods : Patients aged 18 years or older with advanced solid tumors refractory to st and ard treatment were recruited .  Regorafenib was administered orally for 21 days on/seven days off in repeating cycles , until discontinuation due to toxicity or tumor progression . Adverse events ( AE ) were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 . Pharmacokinetic profiles were measured after a single dose and on day 21 . Pharmacodynamic and efficacy evaluations included tumor perfusion assessment using dynamic contrast-enhanced MRI , plasma cytokines , and tumor response using RECIST ( v1.0 ) . Results : Fifty-three patients were enrolled into eight cohorts at dose levels from 10 to 220 mg daily . The recommended dose for future studies was determined to be 160 mg daily , with a treatment schedule of 21 days on/seven days off in repeating 28-day cycles . The most common drug-related grade 3 or 4 AEs were dermatologic AEs ( h and –foot skin reaction , rash ) , hypertension , and diarrhea . Pharmacokinetic analysis revealed a similar exposure at steady state for the parent compound and two pharmacologically active metabolites . Tumor perfusion and plasma cytokine analysis showed biologic activity of regorafenib . Three of 47 evaluable patients achieved a partial response ( renal cell carcinoma , colorectal carcinoma , and osteosarcoma ) . Conclusion : Regorafenib showed an acceptable safety profile and preliminary evidence of antitumor activity in patients with solid tumors . Clin Cancer Res ; 18(9 ) ; 2658–67 . © 2012 AACR PURPOSE In a previous study of treatment for advanced colorectal cancer , the LV5FU2 regimen , comprising leucovorin ( LV ) plus bolus and infusional fluorouracil ( 5FU ) every 2 weeks , was superior to the st and ard North Central Cancer Treatment Group/Mayo Clinic 5-day bolus 5FU/LV regimen . This phase III study investigated the effect of combining oxaliplatin with LV5FU2 , with progression-free survival as the primary end point . PATIENTS AND METHODS Four hundred twenty previously untreated patients with measurable disease were r and omized to receive a 2-hour infusion of LV ( 200 mg/m(2)/d ) followed by a 5FU bolus ( 400 mg/m(2)/d ) and 22-hour infusion ( 600 mg/m(2)/d ) for 2 consecutive days every 2 weeks , either alone or together with oxaliplatin 85 mg/m(2 ) as a 2-hour infusion on day 1 . RESULTS Patients allocated to oxaliplatin plus LV5FU2 had significantly longer progression-free survival ( median , 9.0 v 6.2 months ; P = .0003 ) and better response rate ( 50.7 % v 22.3 % ; P = .0001 ) when compared with the control arm . The improvement in overall survival did not reach significance ( median , 16.2 v 14.7 months ; P = . 12 ) . LV5FU2 plus oxaliplatin gave higher frequencies of National Cancer Institute common toxicity criteria grade 3/4 neutropenia ( 41 . 7 % v 5.3 % of patients ) , grade 3/4 diarrhea ( 11.9 % v 5.3 % ) , and grade 3 neurosensory toxicity ( 18.2 % v 0 % ) , but this did not result in impairment of quality of life ( QoL ) . Survival without disease progression or deterioration in global health status was longer in patients allocated to oxaliplatin treatment ( P = .004 ) . CONCLUSION The LV5FU2-oxaliplatin combination seems beneficial as first-line therapy in advanced colorectal cancer , demonstrating a prolonged progression-free survival with acceptable tolerability and maintenance of 
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Subgroup analysis of adverse events showed a different toxicity profile between both drugs .
Conclusion In this indirect comparison , regorafenib and TAS‐102 appeared to have similar efficacy .
However , regorafenib was associated with more toxicity compared with TAS‐102 .
Micro‐ Abstract Regorafenib and TAS‐102 have shown to be superior to placebo in refractory metastatic colorectal cancer .
A systematic review and network meta‐ analysis comparing regorafenib and TAS‐102 showed similar overall survival and progression‐free survival , but regorafenib was associated with more toxicity compared with TAS‐102