***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 Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies PURPOSE For patients with small-cell lung cancer ( SCLC ) , further chemotherapy is routinely considered at relapse after first-line therapy . However , proof of clinical benefit has not been documented . PATIENTS AND METHODS This study r and omly assigned patients with relapsed SCLC not considered as c and i date s for st and ard intravenous therapy to best supportive care ( BSC ) alone ( n = 70 ) or oral topotecan ( 2.3 mg/m2/d , days 1 through 5 , every 21 days )  plus BSC ( topotecan ; n = 71 ) . RESULTS In the intent-to-treat population , survival ( primary end point ) was prolonged in the topotecan group ( log-rank P = .0104 ) . Median survival with BSC was 13.9 weeks ( 95 % CI , 11.1 to 18.6 ) and with topotecan , 25.9 weeks ( 95 % CI , 18.3 to 31.6 ) . Statistical significance for survival was maintained in a subgroup of patients with a short treatment-free interval ( < or = 60 days ) . Response to topotecan was 7 % partial and 44 % stable disease . Patients on topotecan had slower quality of life deterioration and greater symptom control . Principal toxicities with topotecan were hematological : grade 4 neutropenia , 33 % ; grade 4 thrombocytopenia , 7 % ; and grade 3/4 anemia , 25 % . Comparing topotecan with BSC , infection grade 2 was 14 % versus 12 % and sepsis 4 % versus 1 % ; other grade 3/4 events included vomiting 3 % versus 0 , diarrhea 6 % versus 0 , dyspnea 3 % versus 9 % , and pain 3 % versus 6 % . Toxic deaths occurred in four patients ( 6 % ) in the topotecan arm . All cause mortality within 30 days of r and om assignment was 13 % on BSC and 7 % on topotecan . CONCLUSION Chemotherapy with oral topotecan is associated with prolongation of survival and quality of life benefit in patients with relapsed SCLC PURPOSE This phase II study evaluated the safety and efficacy of single-agent amrubicin versus topotecan in patients with small-cell lung cancer ( SCLC ) sensitive to first-line platinum-based chemotherapy . PATIENTS AND METHODS Patients were r and omly assigned 2:1 to amrubicin ( 40 mg/m(2)/d in a 5-minute intravenous [ IV ] infusion , days 1 through 3 , every 21 days ) or topotecan ( 1.5 mg/m(2)/d in a 30-minute IV infusion , days 1 through 5 , every 21 days ) . The primary efficacy end point was overall response rate ( ORR ) for amrubicin . Secondary end points included time to progression , median progression-free survival ( PFS ) , and median overall survival ( OS ) . RESULTS Of 76 patients enrolled , 50 patients were r and omly assigned to amrubicin , and 26 patients were r and omly assigned to topotecan . Amrubicin treatment result ed in a significantly higher ORR than topotecan ( 44 % v 15 % ; P = .021 ) . Median PFS and median OS were 4.5 months and 9.2 months with amrubicin and 3.3 months and 7.6 months with topotecan , respectively . Tolerability was similar with both agents . However , grade 3 or worse neutropenia and thrombocytopenia seemed to be more frequent in the topotecan group as compared with the amrubicin group ( 78 % and 61 % v 61 % and 39 % , respectively ) . CONCLUSION Amrubicin shows promising activity , with an ORR of 44 % compared with an ORR of 15 % for topotecan as second-line treatment in patients with SCLC sensitive to first-line platinum-based chemotherapy . In addition , the safety profiles were comparable ; however , a trend was noted for more frequent grade 3 or worse neutropenia and thrombocytopenia in the topotecan group as compared with the amrubicin group . Additional studies are ongoing OBJECTIVES We conducted an open-label , multicenter , single-arm study to confirm the efficacy and safety of amrubicin ( AMR ) , a topoisomerase II inhibitor , for treating refractory small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS Patients with chemotherapy-refractory SCLC received  40 mg/m(2 ) AMR  for 3 consecutive days , every 21 days . The primary endpoint was the overall response rate ( ORR ) and the secondary endpoints were progression-free survival ( PFS ) , overall survival ( OS ) , and safety . RESULTS Between November 2009 and February 2011 , 82 patients were enrolled . Each patient received a median of four treatment cycles ( range , 1 - 22 cycles ) . ORR was 32.9 % [ P<0.0001 by the exact binomial test for the null hypothesis that ORR ≤ 10 % ; 95 % confidence interval ( CI ) , 22.9 - 44.2 % ] . The median PFS and OS periods were 3.5 months ( 95 % CI , 3.0 - 4.3 months ) and 8.9 months ( 95 % CI , 7.6 - 11.3 months ) , respectively . Significant differences in ORR ( 21.4 % v 45.0 % ; P=0.034 ) , PFS ( median , 2.9 v 5.1 months ; P=0.0009 ) , and OS ( median , 7.9 v 13.1 months ; P=0.0128 ) were observed between patients previously treated with etoposide and others . Neutropenia was the most common grade 3 or 4 adverse events ( 93.9 % ) , and febrile neutropenia developed in 26.8 % patients . No treatment-related death occurred . CONCLUSIONS AMR monotherapy can be considered an effective and safe treatment option for refractory SCLC . Previous chemotherapy with etoposide may influence AMR efficacy PURPOSE Amrubicin , a third-generation anthracycline and potent topoisomerase II inhibitor , showed promising activity in small-cell lung cancer ( SCLC ) in phase II trials . This phase III trial compared the safety and efficacy of amrubicin versus topotecan as second-line treatment for SCLC . PATIENTS AND METHODS A total of 637 patients with refractory or sensitive SCLC were r and omly assigned at a ratio of 2:1 to 21-day cycles of amrubicin 40 mg/m(2 ) intravenously ( IV ) on days 1 to 3 or topotecan 1.5 mg/m(2 ) IV on days 1 to 5 . Primary end point was overall survival ( OS ) ; secondary end points included overall response rate ( ORR ) , progression-free survival ( PFS ) , and safety . RESULTS Median OS was 7.5 months with amrubicin versus 7.8 months with topotecan ( hazard ratio [ HR ] , 0.880 ; P = .170 ) ; in refractory patients , median OS was 6.2 and 5.7 months , respectively ( HR , 0.77 ; P = .047 ) . Median PFS was 4.1 months with amrubicin and 3.5 months with topotecan ( HR , 0.802 ; P = .018 ) . ORR was 31.1 % with amrubicin and 16.9 % with topotecan ( odds ratio , 2.223 ; P < .001 ) . Grade ≥ 3 treatment-emergent adverse events in the amrubicin and topotecan arms were : neutropenia ( 41 % v 54 % ; P = .004 ) , thrombocytopenia ( 21 % v 54 % ; P < .001 ) , anemia ( 16 % v 31 % ; P < .001 ) , infections ( 16 % v 10 % ; P = .043 ) , febrile neutropenia ( 10 % v 3 % ; P = .003 ) , and cardiac disorders ( 5 % v 5 % ; P = .759 ) ; transfusion rates were 32 % and 53 % ( P < .001 ) , respectively . NQO1 polymorphisms did not influence safety outcomes . CONCLUSION Amrubicin did not improve survival when compared with topotecan in the second-line treatment of patients with SCLC . OS did not differ significantly between treatment groups , although an improvement in OS was noted in patients with refractory disease treated with amrubicin PURPOSE Amrubicin and re-challenge of platinum doublet are both effective treatments for sensitive-relapsed small-cell lung cancer ( SCLC ) . However , no comparative study of these treatments has been reported . This r and omized study was conducted to select the most suitable regimen for future evaluation . PATIENTS AND METHODS SCLC patients who had relapsed more than 90 days after their first-line platinum-doublet regimen were r and omized to receive amrubicin ( 40mg/m(2 ) , days 1 - 3 ) or re-challenge with platinum doublet . Primary endpoint was objective response rate ( ORR ) , with secondary endpoints of progression-free survival ( PFS ) , overall survival and toxicity profiles . We assumed that an ORR of 50 % indicates potential usefulness , while that of 30 % would constitute the lower limit of interest ( alpha 0.1 ; beta 0.1 ) . Initial estimated accrual was 28 patients to each arm . RESULTS From February 2008 to June 2013 , 60 patients were enrolled and 57 patients ( 27 amrubicin and 30 re-challenge ) were found to be evaluable for efficacy and safety . The ORR and PFS were 67 % ( 90 % confidence interval , 52 - 82 ) and 5.4 months in the amrubicin group , and 43 % ( 90 % confidence interval , 28 - 58 ) and 5.1 months in the re-challenge group , respectively . Although grade 3 febrile neutropenia was observed in 19 % of patients in the amrubicin group , these episodes were transient and manageable . Non-hematological toxicities were generally moderate and no treatment-related death was observed in either group . CONCLUSION Only amrubicin met the primary endpoint . Moreover , amrubicin demonstrated superior efficacy over re-challenge of platinum with acceptable levels of toxicity . Further evaluation of amrubicin 
    Output:
    
Amrubicin seemed much more beneficial for Japanese patients .
However , compared to the efficacy of topotecan presented in a previous meta- analysis , amrubicin may be a better treatment option than topotecan for both Japanese and Euro-American .
Adverse effects by amrubicin were almost exclusively observed to be hematological .