human
***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 To know the effectiveness and tolerance of weekly cisplatin added to radiotherapy ( RT ) in advanced carcinoma of oropharynx and nasopharynx . PATIENTS AND METHODS Stage II-IV cancer patients were r and omly assigned to either radical RT , 70 Gy/35 fractions over 7 weeks ( RT arm ) , or chemoradiotherapy ( CRT ) , cisplatin 40 mg/m² weekly for seven doses plus RT . Primary end points were ( i ) the responses , ( ii ) toxicity profile , and ( iii ) overall survival ( OS ) in two groups . Study period was from June 2003 to July 2005 . RESULTS One hundred and fifty-three patients were r and omly allocated to the study , 76 in RT arm and 77 in CRT arm . Seventy-one in each arm completed the planned treatment ; complete response ( CR ) : 67.1 % versus 80.5 % in RT and CRT arms ( P = 0.04 ) . Grade III and IV toxicity were 16 % and 40 % in RT and CRT arms , respectively ( P = 0.01 ) . There were frequent treatment interruptions ( 9.3 % versus 28.9 % ; P = 0.003 ) and hospitalization ( 20 % versus 40.8 % ) in the CRT group . OS was superior in the CRT arm ( P = 0.02 ) : 27 months [ 95 % confidence interval ( CI ) 15.2 - 36.8 ] for RT versus not reached for CRT . Three-year OS was 42 % for RT and 62 % for CRT group . CRT and CR were independent prognostic factors . CONCLUSION This trial on Indian head and neck squamous cell carcinoma patients confirms that the use of weekly cisplatin is safe and CRT is superior to RT alone result ing in higher OS Abstract Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel .  Grade 3 to 4 ( G3–4 ) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer ( TROPIC ) trial , but their incidence was lower in the Exp and ed Access Program ( EAP ) . Although cumulative doses of docetaxel are associated with neuropathy , the effect of cumulative doses of cabazitaxel is unknown . In this retrospective review of prospect ively collected data , the authors assessed “ per cycle ” incidence and predictors of toxicity in the Italian cohort of the EAP , with a focus on the effect of cumulative doses of cabazitaxel . The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP . The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis .“Per cycle ” incidence of G 3 to 4 neutropenia was 8.7 % , whereas febrile neutropenia was reported in 0.9 % of cycles . All events of febrile neutropenia occurred during the first 3 cycles . Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia ( OR = 0.90 ; 95 % CI : 0.86–0.93 ; P < 0.01 ) , febrile neutropenia ( OR = 0.52 ; 95 % CI : 0.34–0.81 ; P < 0.01 ) and G3 to 4 anemia ( OR = 0.93 ; 95 % CI : 0.86–1 ; P = 0.07 ) . Patients with a body surface area > 2 m2 presented increased odds of having G 3 to 4 neutropenia ( OR = 0.93 ; 95 % CI : 0.86–1 ; P = 0.07 ) , but decreased odds of having G3 to 4 anemia . Among the toxicities assessed , the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered . Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia . The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation . Because this analysis is limited by its retrospective design , prospect i ve trials are required to assess the optimal duration of cabazitaxel treatment OBJECTIVE The 7-year follow-up of the US oncology 9735 trial demonstrated the superiority of TC [ docetaxel (DTX)/cyclophosphamide ( CPA ) ] to doxorubicin/CPA therapy . To introduce TC therapy in Japan , the verification of the safety and tolerability is essential . We performed a collaborative prospect i ve safety study with Okayama University to introduce TC therapy . METHODS The subjects were 53 patients aged from 33 to 67 years at intermediate risk based on the St Gallen risk classification who underwent radical surgery for primary breast cancer between August 2007 and December 2008 . As post-operative adjuvant chemotherapy , four cycles of TC ( DTX 75 mg/m(2 ) + CPA 600 mg/m(2 ) ) were administered at 3-week intervals . Adverse events were evaluated based on National Cancer Institute-Common Terminology Criteria for Adverse Events ver . 3.0 . The safety and completion rate were evaluated as the primary and secondary endpoints , respectively . RESULTS Regarding hematological toxicity , Grade ( G ) 4 neutropenia occurred in 71.7 % and G3 in 26.4 % . G3 - 4 leukopenia developed in 32.1 % and 56.6 % , respectively , G4 anemia in 1.9 % and G1 - 2 anemia in 26.4 % . Regarding non-hematological toxicity , systemic malaise , skin eruption , edema , myalgia , arthralgia and nausea were noted in most patients . The completion rate was 94.3 % , dose reduction was necessary in 7.5 % and granulocyte colony-stimulating factor ( G-CSF ) support was required in 17.0 % . On comparison between patients aged 65 years or older and younger than 65 years , the completion rate , dose reduction and incidence of febrile neutropenia ( FN ) were higher in the elderly patients . G-CSF support was more often needed in this subgroup . CONCLUSIONS TC therapy is tolerable for Japanese patients , but attention should be paid to the development of FN and neutropenia . The completion rate was lower in the elderly patients , showing that tolerability was not necessarily favorable BACKGROUND This study aim ed to determine the clinical benefit of neoadjuvant methotrexate , doxorubicin , vinblastine , and cisplatin ( MVAC ) in patients with muscle-invasive bladder cancer ( MIBC ) treated with radical cystectomy . PATIENTS AND METHODS Patients with MIBC ( T2 - 4aN0M0 ) were r and omised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy ( NAC arm ) or radical cystectomy alone ( RC arm ) . The primary end point was overall survival ( OS ) . Secondary end points were progression-free survival , surgery-related complications , adverse events during chemotherapy , proportion with no residual tumour in the cystectomy specimens , and quality of life . To detect an improvement in 5-year OS from 45 % in the RC arm to 57 % in the NAC arm with 80 % power , 176 events were required per arm . RESULTS Patients ( N = 130 ) were r and omly assigned to the RC arm ( N = 66 ) and the NAC arm ( N = 64 ) . The patient registration was terminated before reaching the initially planned number of patients because of slow accrual . At the second interim analysis just after the early stoppage of patient accrual , the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion . OS of the NAC arm was better than that of the RC arm , although the difference was not statistically significant [ hazard ratio 0.65 , multiplicity adjusted 99.99 % confidence interval 0.19 - 2.18 , one-sided P = 0.07 ] . In the NAC arm and the RC arm , 34 % and 9 % of the patients had pT0 , respectively ( P < 0.01 ) . In subgroup analyses , OS in almost all subgroups was in favour of NAC . CONCLUSIONS This trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC . NAC with MVAC can still be considered promising as a st and ard treatment . UMIN CLINICAL TRIALS REGISTRY IDENTIFIER C000000093 PURPOSE This multicenter , r and omized trial compared capecitabine plus oxaliplatin ( XELOX ) with bolus fluorouracil ( FU ) and folinic acid ( FA ) as adjuvant therapy for patients with stage III colon cancer . PATIENTS AND METHODS Patients who had undergone curative resection were r and omly assigned to XELOX ( oxaliplatin 130 mg/m(2 ) on day 1 plus capecitabine 1,000 mg/m(2 ) twice daily on days 1 to 14 every 3 weeks for 24 weeks ) or a st and ard bolus FU/FA adjuvant regimen ( Mayo Clinic for 24 weeks or Roswell Park for 32 weeks ) . The primary study end point was disease-free survival ( DFS ) . RESULTS The intention-to-treat population comprised 1,886 patients ; 944 patients were r and omly assigned to XELOX and 942 to FU/FA ( Mayo Clinic , n = 664 ; Roswell Park , n = 278 ) . After 57 months of follow-up for the primary analysis , 295 patients ( 31.3 % ) in the XELOX group had relapsed , developed a new primary colon cancer , or died compared with 353 patients ( 37.5 % ) in the FU/FA group ( hazard ratio [ HR ] for DFS , 0.80 ; 95 % CI , 0.69 to 0.93 ; P = .0045 ) . The 3-year DFS rate was 70.9 % with XELOX and 66.5 % with FU/FA . The HR for overall survival ( OS ) for XELOX compared to FU/FA was 0.87 ( 95 % CI , 0.72 to 1.05 ; P = .1486 ) . The 5-year OS for XELOX and FU/FA were 77.6 % and 74.2 % , respectively . Follow-up is ongoing . Preplanned multivariate and subgroup analyses supported the robustness of these findings . CONCLUSION The addition of oxaliplatin to capecitabine improves DFS in patients with stage III colon cancer . XELOX is an additional adjuvant treatment option for these patients Background Evidence that chemotherapy improves survival and quality of life in patients with stage IIIB & IV non small cell lung cancer ( NSCLC ) is based on large r and omized controlled trials . The purpose of this study was to determine eligibility of patients with advanced NSCLC for major chemotherapy trials . Methods Physicians treating stage IIIB/IV NSCLC at Sydney Cancer Centre assessed patient eligibility for the E1594 , SWOG9509 and TAX326 trials for patients presenting from October 2001 to December 2002 . A review of the centre 's registry was used to obtain missing data . Results 199 patients with advanced NSCLC were registered during the 14-month period . Characteristics of 100 patients were defined prospect ively , 85 retrospectively : 77 % males , median age 68 ( range 32–88 ) , 64 % stage IV disease . Only 35 % met trial eligibility for E1594 and 28 % for SWOG9509 and TAX326 . Common reasons for in eligibility were : co-morbidities 75(40 % ) ; ECOG Performance Status ≥2 72(39 % ) ; symptomatic brain metastasis 15(8 % ) ; and previous cancers 21(11 % ) . Many patients were ineligible by more than one criterion . Conclusion The majority of patients with advanced NSCLC were ineligible for the large chemotherapy trials . The applicability of trial results to advanced lung cancer population s may be limited . Future trials should be conducted in a more representative population PURPOSE The Arimidex , Tamoxifen Alone or in Combination ( ATAC ) study was a double-blind r and omized trial in which postmenopausal women with early-stage breast cancer were assigned to receive anastrozole , tamoxifen , or the combination . We have conducted a retrospective analysis to examine the effects of comorbidities and age on treatment received , breast cancer-related mortality , and competing causes of mortality . PATIENTS AND METHODS The current analyses were based on 10-year median follow-up data in the two monotherapy arms ( anastrozole  , n = 3,092  ; tamoxifen  , n = 3,094 ) of the ATAC study . Baseline comorbidities and tumor and treatment characteristics were compared between women age less than 70 years and women age 
    Output:
    
agent
This review shows that a significant proportion of patients in curative-intent clinical trials experience toxicities that result in dose modifications-dose reduction , dose delays or missed doses-despite strict selection criteria and intense monitoring .
***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 To know the effectiveness and tolerance of weekly cisplatin added to radiotherapy ( RT ) in advanced carcinoma of oropharynx and nasopharynx . PATIENTS AND METHODS Stage II-IV cancer patients were r and omly assigned to either radical RT , 70 Gy/35 fractions over 7 weeks ( RT arm ) , or chemoradiotherapy ( CRT ) , cisplatin 40 mg/m² weekly for seven doses plus RT . Primary end points were ( i ) the responses , ( ii ) toxicity profile , and ( iii ) overall survival ( OS ) in two groups . Study period was from June 2003 to July 2005 . RESULTS One hundred and fifty-three patients were r and omly allocated to the study , 76 in RT arm and 77 in CRT arm . Seventy-one in each arm completed the planned treatment ; complete response ( CR ) : 67.1 % versus 80.5 % in RT and CRT arms ( P = 0.04 ) . Grade III and IV toxicity were 16 % and 40 % in RT and CRT arms , respectively ( P = 0.01 ) . There were frequent treatment interruptions ( 9.3 % versus 28.9 % ; P = 0.003 ) and hospitalization ( 20 % versus 40.8 % ) in the CRT group . OS was superior in the CRT arm ( P = 0.02 ) : 27 months [ 95 % confidence interval ( CI ) 15.2 - 36.8 ] for RT versus not reached for CRT . Three-year OS was 42 % for RT and 62 % for CRT group . CRT and CR were independent prognostic factors . CONCLUSION This trial on Indian head and neck squamous cell carcinoma patients confirms that the use of weekly cisplatin is safe and CRT is superior to RT alone result ing in higher OS Abstract Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel .  Grade 3 to 4 ( G3–4 ) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer ( TROPIC ) trial , but their incidence was lower in the Exp and ed Access Program ( EAP ) . Although cumulative doses of docetaxel are associated with neuropathy , the effect of cumulative doses of cabazitaxel is unknown . In this retrospective review of prospect ively collected data , the authors assessed “ per cycle ” incidence and predictors of toxicity in the Italian cohort of the EAP , with a focus on the effect of cumulative doses of cabazitaxel . The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP . The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis .“Per cycle ” incidence of G 3 to 4 neutropenia was 8.7 % , whereas febrile neutropenia was reported in 0.9 % of cycles . All events of febrile neutropenia occurred during the first 3 cycles . Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia ( OR = 0.90 ; 95 % CI : 0.86–0.93 ; P < 0.01 ) , febrile neutropenia ( OR = 0.52 ; 95 % CI : 0.34–0.81 ; P < 0.01 ) and G3 to 4 anemia ( OR = 0.93 ; 95 % CI : 0.86–1 ; P = 0.07 ) . Patients with a body surface area > 2 m2 presented increased odds of having G 3 to 4 neutropenia ( OR = 0.93 ; 95 % CI : 0.86–1 ; P = 0.07 ) , but decreased odds of having G3 to 4 anemia . Among the toxicities assessed , the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered . Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia . The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation . Because this analysis is limited by its retrospective design , prospect i ve trials are required to assess the optimal duration of cabazitaxel treatment OBJECTIVE The 7-year follow-up of the US oncology 9735 trial demonstrated the superiority of TC [ docetaxel (DTX)/cyclophosphamide ( CPA ) ] to doxorubicin/CPA therapy . To introduce TC therapy in Japan , the verification of the safety and tolerability is essential . We performed a collaborative prospect i ve safety study with Okayama University to introduce TC therapy . METHODS The subjects were 53 patients aged from 33 to 67 years at intermediate risk based on the St Gallen risk classification who underwent radical surgery for primary breast cancer between August 2007 and December 2008 . As post-operative adjuvant chemotherapy , four cycles of TC ( DTX 75 mg/m(2 ) + CPA 600 mg/m(2 ) ) were administered at 3-week intervals . Adverse events were evaluated based on National Cancer Institute-Common Terminology Criteria for Adverse Events ver . 3.0 . The safety and completion rate were evaluated as the primary and secondary endpoints , respectively . RESULTS Regarding hematological toxicity , Grade ( G ) 4 neutropenia occurred in 71.7 % and G3 in 26.4 % . G3 - 4 leukopenia developed in 32.1 % and 56.6 % , respectively , G4 anemia in 1.9 % and G1 - 2 anemia in 26.4 % . Regarding non-hematological toxicity , systemic malaise , skin eruption , edema , myalgia , arthralgia and nausea were noted in most patients . The completion rate was 94.3 % , dose reduction was necessary in 7.5 % and granulocyte colony-stimulating factor ( G-CSF ) support was required in 17.0 % . On comparison between patients aged 65 years or older and younger than 65 years , the completion rate , dose reduction and incidence of febrile neutropenia ( FN ) were higher in the elderly patients . G-CSF support was more often needed in this subgroup . CONCLUSIONS TC therapy is tolerable for Japanese patients , but attention should be paid to the development of FN and neutropenia . The completion rate was lower in the elderly patients , showing that tolerability was not necessarily favorable BACKGROUND This study aim ed to determine the clinical benefit of neoadjuvant methotrexate , doxorubicin , vinblastine , and cisplatin ( MVAC ) in patients with muscle-invasive bladder cancer ( MIBC ) treated with radical cystectomy . PATIENTS AND METHODS Patients with MIBC ( T2 - 4aN0M0 ) were r and omised to receive two cycles of neoadjuvant MVAC followed by radical cystectomy ( NAC arm ) or radical cystectomy alone ( RC arm ) . The primary end point was overall survival ( OS ) . Secondary end points were progression-free survival , surgery-related complications , adverse events during chemotherapy , proportion with no residual tumour in the cystectomy specimens , and quality of life . To detect an improvement in 5-year OS from 45 % in the RC arm to 57 % in the NAC arm with 80 % power , 176 events were required per arm . RESULTS Patients ( N = 130 ) were r and omly assigned to the RC arm ( N = 66 ) and the NAC arm ( N = 64 ) . The patient registration was terminated before reaching the initially planned number of patients because of slow accrual . At the second interim analysis just after the early stoppage of patient accrual , the Data and Safety Monitoring Committee recommended early publication of the results because the trial did not have enough power to draw a confirmatory conclusion . OS of the NAC arm was better than that of the RC arm , although the difference was not statistically significant [ hazard ratio 0.65 , multiplicity adjusted 99.99 % confidence interval 0.19 - 2.18 , one-sided P = 0.07 ] . In the NAC arm and the RC arm , 34 % and 9 % of the patients had pT0 , respectively ( P < 0.01 ) . In subgroup analyses , OS in almost all subgroups was in favour of NAC . CONCLUSIONS This trial showed a significantly increased pT0 proportion and favourable OS of patients who received neoadjuvant MVAC . NAC with MVAC can still be considered promising as a st and ard treatment . UMIN CLINICAL TRIALS REGISTRY IDENTIFIER C000000093 PURPOSE This multicenter , r and omized trial compared capecitabine plus oxaliplatin ( XELOX ) with bolus fluorouracil ( FU ) and folinic acid ( FA ) as adjuvant therapy for patients with stage III colon cancer . PATIENTS AND METHODS Patients who had undergone curative resection were r and omly assigned to XELOX ( oxaliplatin 130 mg/m(2 ) on day 1 plus capecitabine 1,000 mg/m(2 ) twice daily on days 1 to 14 every 3 weeks for 24 weeks ) or a st and ard bolus FU/FA adjuvant regimen ( Mayo Clinic for 24 weeks or Roswell Park for 32 weeks ) . The primary study end point was disease-free survival ( DFS ) . RESULTS The intention-to-treat population comprised 1,886 patients ; 944 patients were r and omly assigned to XELOX and 942 to FU/FA ( Mayo Clinic , n = 664 ; Roswell Park , n = 278 ) . After 57 months of follow-up for the primary analysis , 295 patients ( 31.3 % ) in the XELOX group had relapsed , developed a new primary colon cancer , or died compared with 353 patients ( 37.5 % ) in the FU/FA group ( hazard ratio [ HR ] for DFS , 0.80 ; 95 % CI , 0.69 to 0.93 ; P = .0045 ) . The 3-year DFS rate was 70.9 % with XELOX and 66.5 % with FU/FA . The HR for overall survival ( OS ) for XELOX compared to FU/FA was 0.87 ( 95 % CI , 0.72 to 1.05 ; P = .1486 ) . The 5-year OS for XELOX and FU/FA were 77.6 % and 74.2 % , respectively . Follow-up is ongoing . Preplanned multivariate and subgroup analyses supported the robustness of these findings . CONCLUSION The addition of oxaliplatin to capecitabine improves DFS in patients with stage III colon cancer . XELOX is an additional adjuvant treatment option for these patients Background Evidence that chemotherapy improves survival and quality of life in patients with stage IIIB & IV non small cell lung cancer ( NSCLC ) is based on large r and omized controlled trials . The purpose of this study was to determine eligibility of patients with advanced NSCLC for major chemotherapy trials . Methods Physicians treating stage IIIB/IV NSCLC at Sydney Cancer Centre assessed patient eligibility for the E1594 , SWOG9509 and TAX326 trials for patients presenting from October 2001 to December 2002 . A review of the centre 's registry was used to obtain missing data . Results 199 patients with advanced NSCLC were registered during the 14-month period . Characteristics of 100 patients were defined prospect ively , 85 retrospectively : 77 % males , median age 68 ( range 32–88 ) , 64 % stage IV disease . Only 35 % met trial eligibility for E1594 and 28 % for SWOG9509 and TAX326 . Common reasons for in eligibility were : co-morbidities 75(40 % ) ; ECOG Performance Status ≥2 72(39 % ) ; symptomatic brain metastasis 15(8 % ) ; and previous cancers 21(11 % ) . Many patients were ineligible by more than one criterion . Conclusion The majority of patients with advanced NSCLC were ineligible for the large chemotherapy trials . The applicability of trial results to advanced lung cancer population s may be limited . Future trials should be conducted in a more representative population PURPOSE The Arimidex , Tamoxifen Alone or in Combination ( ATAC ) study was a double-blind r and omized trial in which postmenopausal women with early-stage breast cancer were assigned to receive anastrozole , tamoxifen , or the combination . We have conducted a retrospective analysis to examine the effects of comorbidities and age on treatment received , breast cancer-related mortality , and competing causes of mortality . PATIENTS AND METHODS The current analyses were based on 10-year median follow-up data in the two monotherapy arms ( anastrozole  , n = 3,092  ; tamoxifen  , n = 3,094 ) of the ATAC study . Baseline comorbidities and tumor and treatment characteristics were compared between women age less than 70 years and women age 
    Output:
    