***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: Aim : S-1 is an oral anticancer fluoropyrimidine formulation consisting of tegafur , 5-chloro-2,4-dihydroxypyridine and potassium oxonate . The aim of this study was to evaluate the pharmacokinetics and bioequivalence of a newly developed generic formulation of S-1 in Chinese cancer patients in comparison with the br and ed reference formulation of S-1 . Methods : A single-dose , r and omized-sequence , open-label , two-way self-crossover study was conducted in 30 Chinese cancer patients . The subjects alternatively received the two formulations ( 40 mg/m2 , po ) with a 7-d interval . Plasma concentrations of FT , CDHP , Oxo , and 5-Fu were determined using LC-MS/MS . Pharmacokinetic parameters , including Cmax , Tmax , t1/2 , AUC0–t , and AUC0–∞ were determined using non-compartmental models with DAS2.0 software . Bioequivalence of the two formulations were to be evaluated according to 90 % CIs for the log-transformed ratios of AUC and Cmax of S-1 . Adverse events were evaluated through monitoring the symptom , physical and laboratory examinations , ECGs and subject interviews . Results : The mean values of Cmax , AUC0–t , and AUC0–∞ of FT , 5-Fu , CDHP , and Oxo for the two formulations had no significant differences . The 90 % CIs for natural log-transformed ratios of Cmax , AUC0–t , and AUC0–∞ were within the predetermined bioequivalence acceptance limits . A total of 11 mild adverse events , including fatigue , nausea and vomiting , anorexia , diarrhea and myelosuppression , were observed , and no serious and special adverse events were found . Conclusion : The newly developed generic formulation and reference formulation of S-1 have similar pharmacokinetics with one dose ( 40 mg/m2 ) in Chinese cancer patients . Both the formulations of S-1 are well tolerated The prognosis of patients with hepatocellular carcinoma ( HCC ) with portal vein tumor thrombosis ( PVTT ) is extremely poor . The aim of this study was to eluci date the efficacy of hepatic arterial infusion chemotherapy ( HAIC ) for patients with advanced HCCs S‐1 , an oral fluoropyrimidine derivative , has been shown to be clinical ly effective against various solid tumors , and pre clinical studies have demonstrated activity against hepatocellular carcinoma . We conducted a phase I/II study in patients with advanced hepatocellular carcinoma to examine the pharmacokinetics , recommended dose , safety and efficacy of S‐1 . In phase I , the administered dose of S‐1 was approximately 64 mg/m2 per day in three patients ( level 1 ) and approximately 80 mg/m2 per day in six patients ( level 2 ) . There was no dose‐limiting toxicity at level 1 , but two patients had dose‐limiting toxicity at level 2 ( grade 3 anorexia and grade 2 rash requiring eight or more consecutive days of rest ) . The recommended dose was finally estimated to be 80 mg/m2 per day . There were no significant differences in the pharmacokinetics of S‐1 between patients with Child‐Pugh A and those with B. In phase II , five of 23 patients ( 21.7 % ) had partial responses . The median progression‐free survival and overall survival were 3.7 and 16.6 months , respectively . The most common toxicities of grade 3 or 4 were elevated serum aspartate aminotransferase levels , hypochromia and thrombocytopenia . In conclusion , S‐1 showed an acceptable toxicity profile and promising antitumor activity for hepatocellular carcinoma , warranting further evaluation in r and omized clinical trials . ( Cancer Sci 2010 ; 101 : 2606–2611 Purpose Although several clinical trials have proven the efficacy of adjuvant S-1 treatment in gastric cancers , it is still unclear which patients receive the most benefit . In this study , we prospect ively recruited patients with locally advanced gastric cancer who had undergone curative resection followed by adjuvant S-1 administration  to investigate which factors affect the outcomes . Material s and Methods Between July 2010 and October 2011 , we enrolled 49 patients who underwent curative resection for stage II or III gastric cancer and who subsequently received adjuvant S-1 treatment for 1 year . Results Twenty-nine patients ( 59.2 % ) continued S-1 treatment for 1 year , and 12 patients ( 24.5 % ) experienced recurrent disease during the follow-up period . Patients with continuation of S-1 for 1 year had significantly increased rates of disease-free survival ( P<0.001 ) and overall survival ( P=0.001 ) relative to the patients who discontinued S-1 during year 1 . Multivariate analysis indicated poor outcomes for patients with stage III disease and those who discontinued S-1 treatment . Excluding patients who discontinued S-1 due to cancer progression ( n=7 ) , adjuvant treatment with S-1 still demonstrated a significant difference in the disease-free survival rate between the patients who continued treatment and those who discontinued it ( P=0.020 ) . Conclusions S-1 is tolerated as adjuvant treatment in gastric cancer patients . However , discontinuing S-1 treatment may be an unfavorable factor in the prevention of recurrence . S-1 adjuvant treatment should be continued for 1 year if possible through the proper management of toxicities Hepatocellular carcinoma ( HCC ) with portal venous invasion ( PVI ) has a very poor prognosis , with a median survival of 3 months and virtually no survival at 1 year . The combination of intraarterial 5‐fluorouracil ( FU ) and systemic interferon‐α ( IFNα ) was recently reported to be effective against HCC with PVI , but these were small pilot studies BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important . We did a multinational phase III , r and omised , double-blind , placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced ( unresectable or metastatic ) hepatocellular carcinoma . METHODS Between Sept 20 , 2005 , and Jan 31 , 2007 , patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A , were r and omly assigned to receive either oral sorafenib ( 400 mg ) or placebo twice daily in 6-week cycles , with efficacy measured at the end of each 6-week period . Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread ( or both ) , Eastern Cooperative Oncology Group performance status , and geographical region . R and omisation was done central ly and in a 2:1 ratio by means of an interactive voice-response system . There was no predefined primary endpoint ; overall survival , time to progression ( TTP ) , time to symptomatic progression ( TTSP ) , disease control rate ( DCR ) , and safety were assessed . Efficacy analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00492752 . FINDINGS 271 patients from 23 centres in China , South Korea , and Taiwan were enrolled in the study . Of these , 226 patients were r and omly assigned to the experimental group ( n=150 ) or to the placebo group ( n=76 ) . Median overall survival was 6.5 months ( 95 % CI 5.56 - 7.56 ) in patients treated with sorafenib , compared with 4.2 months ( 3.75 - 5.46 ) in those who received placebo ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.50 - 0.93 ] ; p=0.014 ) . Median TTP was 2.8 months ( 2.63 - 3.58 ) in the sorafenib group compared with 1.4 months ( 1.35 - 1.55 ) in the placebo group ( HR 0.57 [ 0.42 - 0.79 ] ; p=0.0005 ) . The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were h and -foot skin reaction ( HFSR ; 16 patients [ 10.7 % ] ) , diarrhoea ( nine patients [ 6.0 % ] ) , and fatigue ( five patients [ 3.4 % ] ) . The most common adverse events result ing in dose reductions were HFSR ( 17 patients [ 11.4 % ] ) and diarrhoea ( 11 patients [ 7.4 % ] ) ; these adverse events rarely led to discontinuation . INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region , and is well tolerated . Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment R and omised Protocol ( SHARP ) trial , sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma Although transcatheter arterial chemoembolization ( TACE ) is considered to be an effective treatment for advanced hepatocellular carcinoma ( HCC ) , it is difficult to achieve complete necrosis by TACE alone due to incomplete embolization and tumor angiogenesis . Recent studies have shown that tegafur/uracil ( UFT ) inhibits tumor angiogenesis in several cancer types . Therefore , this study was conducted to test the efficacy and toxicity of the UFT administration after TACE in advanced HCC . Thirty patients with HCC who had been treated with TACE alone more than three times and had a recurrence within 6 months were enrolled . All of the patients were treated with TACE and 28 patients were r and omly assigned to the UFT ( UFT 300 mg/day , three days after TACE , n=14 ) and control groups ( n=14 ) . The primary end point was the time to treatment failure ( TTF ) and the secondary end points were mainly the response rate and toxicity . Administration and observation were continued up to 6 months after TACE unless local recurrence was detected or serious adverse events developed . The median TTF in the control group was 87 days , whereas in the UFT group it was 127 days , thus significantly prolonged as compared to the control group ( P=0.0016 ) . Moreover , the overall response rate ( 35.7 % ) in the UFT group was significantly higher than that in the control group ( 0 % ) . As for toxicity , only 4 patients in the UFT group developed grade 1 - 2 toxicities such as ascites . Serious complications by TACE were not observed in either group . Notably , there were no increases in the serum VEGF levels in the UFT group whereas those in the control group increased significantly . In conclusion , UFT administration after TACE was an effective treatment and showed no severe adverse events . This regimen may have an adjuvant role and antiangiogenic function in advanced HCC 
    Output:
    
The current evidence from the available clinical studies suggests that S-1 may be an effective and tolerable treatment for advanced HCC .