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: A phase III r and omized trial was conducted to investigate whether induction chemotherapy followed by radiation can influence survival as compared with radiation alone in unresectable , locally advanced non-small-cell lung cancer ( LADNSCLC ) . A total of 101 patients with unresectable stage IIIA or IIIB NSCLC were enrolled . Patients were stratified by performance status , weight loss , histology and stage , and then r and omized to receive combined chemoradiotherapy or radiotherapy alone . Radiotherapy was administered in 1.8 Gy to 2.0 Gy st and ard fractions daily 5 times weekly for a total dose of 60 Gy to 65 Gy . The combined group received induction of cisplatin , etoposide , and vinblastine ( PEV ) chemotherapy with cisplatin 20 mg/m2 on days 1 to 5 , etoposide 100 mg/m2 on days 2 to 4 , and vinblastine 6 mg/m2 on day 1 , which wasrepeated every 3 weeks for 3 courses , after which time the patients underwent radiotherapy .  Of 101 patients registered , 89 patients ( 43 combined , 46 radiotherapy alone ) were eligible for analysis . The response rates for the combined and radiotherapy groups were 65 % ( 28/43 ) and 70 % ( 32/46 ) , respectively . The median survival time ( MST ) showed a tendency to be more prolonged in the combined group than in the group receiving radiotherapy alone ( 13.8 vs. 8.5 months ) . The MST in patients with nonsquamous histology was strikingly prolonged in the combined group as compared with the radiotherapy group ( 14 vs. 3.6 months , p 0.027 ) . Likewise , the MST in patients with stage IIIB was significantly prolonged in the combined group as compared with the radiotherapy group ( 11.1 vs. 7.2 months , p 0.045 ) . Together , the MST of the high-risk group with nonsquamous or stage IIIB was significantly higher in the combined group than that seen in the radiotherapy group ( 11.6 vs. 8 months , p 0.046 ) , whereas the MST of the low-risk group , defined as having both squamous histology and stage IIIA , was similar in the two treatment groups ( 18.3 vs. 20.8 months , p = 0.293 ) . In conclusion , induction PEV chemotherapy plus radiotherapy is superior to radiotherapy alone in high-risk subsets of unresectable LAD-NSCLC and therapeutic strategy should be based on the identification of prognostic factors PURPOSE The superiority of chemoradiotherapy ( CRT ) over radiation alone in locally advanced non-small cell lung cancer ( NSCLC ) has been proven , but the relative merits of a concurrent schedule versus their sequential administration are less clear . This study compared the safety and efficacy of concurrent and sequential CRT , with chemotherapy ( CT ) consisting of a cisplatin and vinorelbine regimen , in patients with locally advanced NSCLC . PATIENTS AND METHODS One hundred and two previously untreated patients ( aged 42 - 75 years ) with locally advanced , stage IIIA ( n = 15 ) or stage IIIB ( n = 87 ) NSCLC were entered into the study . The CT schedule consisted of up to four cycles of cisplatin 80 mg/m(2 ) on day 1 , and vinorelbine 25 mg/m(2 ) at the first and fourth cycles ( 12.5 mg/m(2 ) during the 2nd/3rd cycles ) on days 1 , 8 , 15 of a 28-day cycle . Radiotherapy ( RT ) was prescribed at a dose of 60 Gy/30 fractions , given as five fractions per week for 6 weeks . In the concurrent arm ( arm A ) , RT was started on day 4 of cycle 2 ; whilst in the sequential arm ( arm B ) , RT started within 2 weeks after completion of CT . Fifty-two patients were r and omized to concurrent treatment and 50 to the sequential schedule . RESULTS Overall survival was significantly longer in arm A ( median survival 16.6 months ) versus arm B ( median survival 12.9 months ) ( P = 0.023 by means of log-rank test ; hazard ratio HR = 0.61 , 95 % CI of HR ( 0.39 - 0.93 ) ) , and time to progression ( TTP ) was also significantly longer in arm A ( median time to progression 11.9 months ) versus arm B ( median time to progression 8.5 months ) ( P = 0.024 by means of log-rank test ; HR = 0.62 , 95 % CI of HR ( 0.38 - 0.93 ) ) . Ninety-eight patients were evaluable for response and 101 for toxicity .  The overall response rate was significantly higher in arm A , 80 % ( with 21 % complete response ( CR ) ) compared with 47 % ( with 17 % CR ) in arm B ( P = 0.001 by means of chi(2)-test ) . WHO grade 3 or 4 toxicity was more frequent in arm A than in arm B , with a significantly greater incidence of leucopenia ( 53 % versus 19 % , P = 0.009 by means of chi(2 ) test ) and nausea/vomiting ( 39 % versus 15 % , P = 0.044 by means of chi(2 ) test ) . There were no treatment related deaths . CONCLUSION In this study population , concurrent CRT demonstrated significant benefit in terms of response rate , overall survival and time to progression over sequential CRT . The concurrent CRT schedule was associated with higher toxicity ; however , the adverse event profile was acceptable in both arms Results from the multicentre r and omized trial of CHART ( continuous , hyperfractionated , accelerated radiotherapy ) in non-small-cell lung cancer ( NSCLC ) showed a significant increase in survival ( P=0.004 ) compared with conventional radiotherapy and a therapeutic benefit relative to late radiation-induced morbidity . However , 60 % of patients died because of failure to control locoregional disease . These findings have stimulated interest in assessing the feasibility of dose escalation using a modified CHART schedule . Acute and late morbidity with a CHARTWEL ( CHART WeekEnd Less ) schedule of 54 Gy in 16 days was compared with that observed with 60 Gy in 18 days in patients with locally advanced NSCLC . The incidence and severity of dysphagia and of analgesia were scored using a semiquantitative clinical scale . Late radiation-induced morbidity , namely pulmonary , spinal cord and oesophageal strictures , were monitored using clinical and /or radiological criteria . Acute dysphagia and the analgesia required to control the symptoms were more severe and lasted longer in patients treated with CHARTWEL 60 Gy ( P < or = 0.02 ) . However , at 12 weeks , oesophagitis was similar to that seen with 54 Gy and did not lead to consequential damage . Early radiation pneumonitis was not increased but , after 6 months , there was a higher incidence of mild pulmonary toxicity compared with CHARTWEL 54 Gy . No cases of radiation myelitis , oesophageal strictures or of grade 2 or 3 lung morbidity have been encountered . CHARTWEL 60 Gy result ed in an enhancement of oesophagitis and grade 1 lung toxicity compared with CHARTWEL 54 Gy . These were of no clinical significance , but may be important if CHARTWEL is used with concomitant chemotherapy . These results provide a basis for further dose escalation or the introduction of concurrent chemotherapy BACKGROUND Human tumour cells can proliferate rapidly , and giving radiotherapy in many small fractions may reduce long-term normal-tissue morbidity . In response to these observations , we developed the CHART ( continuous hyperfractionated accelerated radiotherapy ) regimen , which uses thirty-six small fractions of 1.5 Gy given three times per day , to give 54 Gy in only 12 consecutive days . We report the long-term follow-up of a trial of CHART versus conventional radiotherapy in patients with locally advanced non-small-cell lung cancer ( NSCLC ) . METHODS 563 patients were entered by thirteen centres between April , 1990 , and March , 1995 . We included patients with NSCLC localised to the chest with a performance status of 0 or 1 in whom radical radiotherapy was chosen as the definitive management . Patients were r and omly allocated in a 3:2 ratio to CHART or conventional radiotherapy . The latter was thirty fractions of 2 Gy to a total dose of 60 Gy in 6 weeks . RESULTS The groups were well matched for possible prognostic factors . Overall there was a 24 % reduction in the relative risk of death , which is equivalent to an absolute improvement in 2-year survival of 9 % from 20 % to 29 % ( p = 0.004 , 95 % CI 0.63 - 0.92 ) . Subgroup analyses ( predefined ) suggest that the largest benefit occurred in patients with squamous cell carcinomas ( 82 % of the cases ) , in whom there was a 34 % reduction in the relative risk of death ( an absolute improvement at 2 years of 14 % from 19 % to 33 % ) . During the first 3 months , severe dysphagia occurred more often in the CHART group than in the group on conventional radiotherapy ( 19 vs 3 % ) . Otherwise , there were no important differences in short-term or long-term morbidity . INTERPRETATION CHART compared with conventional radiotherapy gave a significant improvement in survival of patients with NSCLC . Further improvement may be achieved with dose escalation in conformal radiotherapy , by the addition of cytotoxic chemotherapy , and by hypoxic cell radiosensitisation PURPOSE To evaluate new drugs in combination with cisplatin in unresectable stage III non-small-cell lung cancer , Cancer and Leukemia Group B ( CALGB ) conducted a r and omized phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy . PATIENTS AND METHODS Eligible patients received four cycles of cisplatin at 80 mg/m(2 ) on days 1 , 22 , 43 , and 64 with arm 1 : gemcitabine 1,250 mg/m(2 ) on days 1 , 8 , 22 , and 29 and 600 mg/m(2 ) on days 43 , 50 , 64 , and 71 ; arm 2 : paclitaxel 225 mg/m(2 ) for 3 hours on days 1 and 22 and 135 mg/m(2 ) on days 43 and 64 ; and arm 3 : vinorelbine 25 mg/m(2 ) on days 1 , 8 , 15 , 22 , and 29 and 15 mg/m(2 ) on days 43 , 50 , 64 , and 71 . Radiotherapy was initiated on day 43 at 2 Gy/d ( total dose , 66 Gy ) . RESULTS One hundred seventy-five eligible patients were analyzed . Toxicities during induction chemotherapy consisted primarily of grade 3 or 4 granulocytopenia . Grade 3 or 4 toxicities during concomitant chemoradiotherapy consisted of thrombocytopenia , granulo-cytopenia , and esophagitis . Response rates after completion of radiotherapy were 74 % , 67 % , and 73 % for arms 1 , 2 , and 3 , respectively . Median survival for all patients was 17 months . One- , 2- , and 3-year survival rates for the patients on the three arms were 68%/37%/28 % , 62%/29%/19 % , and 65%/40%/23 % . CONCLUSION Four cycles of gemcitabine , vinorelbine , or paclitaxel in combination with cisplatin can be administered at these doses and schedules . The observed survival rates exceed those of previous CALGB trials and may be attributable to the use of concomitant chemoradiotherapy . Induction chemotherapy added to concomitant chemoradiotherapy is being evaluated in a phase III r and omized trial PURPOSE Chemotherapy for non-small-cell lung cancer ( NSCLC ) remains controversial . We describe the two largest reported , r and omized , parallel trials design ed to determine whether the addition of chemotherapy influences duration and quality of life in localized , unresectable ( mitomycin , ifosfamide ,  cisplatin [MIC]1 trial ) and extensive ( MIC2 trial ) disease . PATIENTS AND METHODS Ambulatory patients with NSCLC , aged 75 years or younger , with localized disease , were r and omized in MIC1 to receive up to four cycles of chemotherapy ( CT : mitomycin 6 mg/m(2 ) , ifosfamide 3 g/m(2 ) , and cisplatin 50 mg/m(2 ) ) every 21 days , followed by radical radiotherapy ( CT + RT ) or radiotherapy ( RT ) alone . Extensive-stage patients were r and omized in MIC2 to identical chemotherapy plus palliative care ( CT + PC ) or palliative care ( PC ) alone . Short-term change in quality of life ( QOL ) was assessed in a subgroup of patients . Data from the two trials were combined to allow multivariate and stratified survival analyses . RESULTS Seven hundred ninety-seven eligible patients were r and omized , 446 in MIC1 and 351 
    Output:
    
agent
***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: A phase III r and omized trial was conducted to investigate whether induction chemotherapy followed by radiation can influence survival as compared with radiation alone in unresectable , locally advanced non-small-cell lung cancer ( LADNSCLC ) . A total of 101 patients with unresectable stage IIIA or IIIB NSCLC were enrolled . Patients were stratified by performance status , weight loss , histology and stage , and then r and omized to receive combined chemoradiotherapy or radiotherapy alone . Radiotherapy was administered in 1.8 Gy to 2.0 Gy st and ard fractions daily 5 times weekly for a total dose of 60 Gy to 65 Gy . The combined group received induction of cisplatin , etoposide , and vinblastine ( PEV ) chemotherapy with cisplatin 20 mg/m2 on days 1 to 5 , etoposide 100 mg/m2 on days 2 to 4 , and vinblastine 6 mg/m2 on day 1 , which wasrepeated every 3 weeks for 3 courses , after which time the patients underwent radiotherapy .  Of 101 patients registered , 89 patients ( 43 combined , 46 radiotherapy alone ) were eligible for analysis . The response rates for the combined and radiotherapy groups were 65 % ( 28/43 ) and 70 % ( 32/46 ) , respectively . The median survival time ( MST ) showed a tendency to be more prolonged in the combined group than in the group receiving radiotherapy alone ( 13.8 vs. 8.5 months ) . The MST in patients with nonsquamous histology was strikingly prolonged in the combined group as compared with the radiotherapy group ( 14 vs. 3.6 months , p 0.027 ) . Likewise , the MST in patients with stage IIIB was significantly prolonged in the combined group as compared with the radiotherapy group ( 11.1 vs. 7.2 months , p 0.045 ) . Together , the MST of the high-risk group with nonsquamous or stage IIIB was significantly higher in the combined group than that seen in the radiotherapy group ( 11.6 vs. 8 months , p 0.046 ) , whereas the MST of the low-risk group , defined as having both squamous histology and stage IIIA , was similar in the two treatment groups ( 18.3 vs. 20.8 months , p = 0.293 ) . In conclusion , induction PEV chemotherapy plus radiotherapy is superior to radiotherapy alone in high-risk subsets of unresectable LAD-NSCLC and therapeutic strategy should be based on the identification of prognostic factors PURPOSE The superiority of chemoradiotherapy ( CRT ) over radiation alone in locally advanced non-small cell lung cancer ( NSCLC ) has been proven , but the relative merits of a concurrent schedule versus their sequential administration are less clear . This study compared the safety and efficacy of concurrent and sequential CRT , with chemotherapy ( CT ) consisting of a cisplatin and vinorelbine regimen , in patients with locally advanced NSCLC . PATIENTS AND METHODS One hundred and two previously untreated patients ( aged 42 - 75 years ) with locally advanced , stage IIIA ( n = 15 ) or stage IIIB ( n = 87 ) NSCLC were entered into the study . The CT schedule consisted of up to four cycles of cisplatin 80 mg/m(2 ) on day 1 , and vinorelbine 25 mg/m(2 ) at the first and fourth cycles ( 12.5 mg/m(2 ) during the 2nd/3rd cycles ) on days 1 , 8 , 15 of a 28-day cycle . Radiotherapy ( RT ) was prescribed at a dose of 60 Gy/30 fractions , given as five fractions per week for 6 weeks . In the concurrent arm ( arm A ) , RT was started on day 4 of cycle 2 ; whilst in the sequential arm ( arm B ) , RT started within 2 weeks after completion of CT . Fifty-two patients were r and omized to concurrent treatment and 50 to the sequential schedule . RESULTS Overall survival was significantly longer in arm A ( median survival 16.6 months ) versus arm B ( median survival 12.9 months ) ( P = 0.023 by means of log-rank test ; hazard ratio HR = 0.61 , 95 % CI of HR ( 0.39 - 0.93 ) ) , and time to progression ( TTP ) was also significantly longer in arm A ( median time to progression 11.9 months ) versus arm B ( median time to progression 8.5 months ) ( P = 0.024 by means of log-rank test ; HR = 0.62 , 95 % CI of HR ( 0.38 - 0.93 ) ) . Ninety-eight patients were evaluable for response and 101 for toxicity .  The overall response rate was significantly higher in arm A , 80 % ( with 21 % complete response ( CR ) ) compared with 47 % ( with 17 % CR ) in arm B ( P = 0.001 by means of chi(2)-test ) . WHO grade 3 or 4 toxicity was more frequent in arm A than in arm B , with a significantly greater incidence of leucopenia ( 53 % versus 19 % , P = 0.009 by means of chi(2 ) test ) and nausea/vomiting ( 39 % versus 15 % , P = 0.044 by means of chi(2 ) test ) . There were no treatment related deaths . CONCLUSION In this study population , concurrent CRT demonstrated significant benefit in terms of response rate , overall survival and time to progression over sequential CRT . The concurrent CRT schedule was associated with higher toxicity ; however , the adverse event profile was acceptable in both arms Results from the multicentre r and omized trial of CHART ( continuous , hyperfractionated , accelerated radiotherapy ) in non-small-cell lung cancer ( NSCLC ) showed a significant increase in survival ( P=0.004 ) compared with conventional radiotherapy and a therapeutic benefit relative to late radiation-induced morbidity . However , 60 % of patients died because of failure to control locoregional disease . These findings have stimulated interest in assessing the feasibility of dose escalation using a modified CHART schedule . Acute and late morbidity with a CHARTWEL ( CHART WeekEnd Less ) schedule of 54 Gy in 16 days was compared with that observed with 60 Gy in 18 days in patients with locally advanced NSCLC . The incidence and severity of dysphagia and of analgesia were scored using a semiquantitative clinical scale . Late radiation-induced morbidity , namely pulmonary , spinal cord and oesophageal strictures , were monitored using clinical and /or radiological criteria . Acute dysphagia and the analgesia required to control the symptoms were more severe and lasted longer in patients treated with CHARTWEL 60 Gy ( P < or = 0.02 ) . However , at 12 weeks , oesophagitis was similar to that seen with 54 Gy and did not lead to consequential damage . Early radiation pneumonitis was not increased but , after 6 months , there was a higher incidence of mild pulmonary toxicity compared with CHARTWEL 54 Gy . No cases of radiation myelitis , oesophageal strictures or of grade 2 or 3 lung morbidity have been encountered . CHARTWEL 60 Gy result ed in an enhancement of oesophagitis and grade 1 lung toxicity compared with CHARTWEL 54 Gy . These were of no clinical significance , but may be important if CHARTWEL is used with concomitant chemotherapy . These results provide a basis for further dose escalation or the introduction of concurrent chemotherapy BACKGROUND Human tumour cells can proliferate rapidly , and giving radiotherapy in many small fractions may reduce long-term normal-tissue morbidity . In response to these observations , we developed the CHART ( continuous hyperfractionated accelerated radiotherapy ) regimen , which uses thirty-six small fractions of 1.5 Gy given three times per day , to give 54 Gy in only 12 consecutive days . We report the long-term follow-up of a trial of CHART versus conventional radiotherapy in patients with locally advanced non-small-cell lung cancer ( NSCLC ) . METHODS 563 patients were entered by thirteen centres between April , 1990 , and March , 1995 . We included patients with NSCLC localised to the chest with a performance status of 0 or 1 in whom radical radiotherapy was chosen as the definitive management . Patients were r and omly allocated in a 3:2 ratio to CHART or conventional radiotherapy . The latter was thirty fractions of 2 Gy to a total dose of 60 Gy in 6 weeks . RESULTS The groups were well matched for possible prognostic factors . Overall there was a 24 % reduction in the relative risk of death , which is equivalent to an absolute improvement in 2-year survival of 9 % from 20 % to 29 % ( p = 0.004 , 95 % CI 0.63 - 0.92 ) . Subgroup analyses ( predefined ) suggest that the largest benefit occurred in patients with squamous cell carcinomas ( 82 % of the cases ) , in whom there was a 34 % reduction in the relative risk of death ( an absolute improvement at 2 years of 14 % from 19 % to 33 % ) . During the first 3 months , severe dysphagia occurred more often in the CHART group than in the group on conventional radiotherapy ( 19 vs 3 % ) . Otherwise , there were no important differences in short-term or long-term morbidity . INTERPRETATION CHART compared with conventional radiotherapy gave a significant improvement in survival of patients with NSCLC . Further improvement may be achieved with dose escalation in conformal radiotherapy , by the addition of cytotoxic chemotherapy , and by hypoxic cell radiosensitisation PURPOSE To evaluate new drugs in combination with cisplatin in unresectable stage III non-small-cell lung cancer , Cancer and Leukemia Group B ( CALGB ) conducted a r and omized phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy . PATIENTS AND METHODS Eligible patients received four cycles of cisplatin at 80 mg/m(2 ) on days 1 , 22 , 43 , and 64 with arm 1 : gemcitabine 1,250 mg/m(2 ) on days 1 , 8 , 22 , and 29 and 600 mg/m(2 ) on days 43 , 50 , 64 , and 71 ; arm 2 : paclitaxel 225 mg/m(2 ) for 3 hours on days 1 and 22 and 135 mg/m(2 ) on days 43 and 64 ; and arm 3 : vinorelbine 25 mg/m(2 ) on days 1 , 8 , 15 , 22 , and 29 and 15 mg/m(2 ) on days 43 , 50 , 64 , and 71 . Radiotherapy was initiated on day 43 at 2 Gy/d ( total dose , 66 Gy ) . RESULTS One hundred seventy-five eligible patients were analyzed . Toxicities during induction chemotherapy consisted primarily of grade 3 or 4 granulocytopenia . Grade 3 or 4 toxicities during concomitant chemoradiotherapy consisted of thrombocytopenia , granulo-cytopenia , and esophagitis . Response rates after completion of radiotherapy were 74 % , 67 % , and 73 % for arms 1 , 2 , and 3 , respectively . Median survival for all patients was 17 months . One- , 2- , and 3-year survival rates for the patients on the three arms were 68%/37%/28 % , 62%/29%/19 % , and 65%/40%/23 % . CONCLUSION Four cycles of gemcitabine , vinorelbine , or paclitaxel in combination with cisplatin can be administered at these doses and schedules . The observed survival rates exceed those of previous CALGB trials and may be attributable to the use of concomitant chemoradiotherapy . Induction chemotherapy added to concomitant chemoradiotherapy is being evaluated in a phase III r and omized trial PURPOSE Chemotherapy for non-small-cell lung cancer ( NSCLC ) remains controversial . We describe the two largest reported , r and omized , parallel trials design ed to determine whether the addition of chemotherapy influences duration and quality of life in localized , unresectable ( mitomycin , ifosfamide ,  cisplatin [MIC]1 trial ) and extensive ( MIC2 trial ) disease . PATIENTS AND METHODS Ambulatory patients with NSCLC , aged 75 years or younger , with localized disease , were r and omized in MIC1 to receive up to four cycles of chemotherapy ( CT : mitomycin 6 mg/m(2 ) , ifosfamide 3 g/m(2 ) , and cisplatin 50 mg/m(2 ) ) every 21 days , followed by radical radiotherapy ( CT + RT ) or radiotherapy ( RT ) alone . Extensive-stage patients were r and omized in MIC2 to identical chemotherapy plus palliative care ( CT + PC ) or palliative care ( PC ) alone . Short-term change in quality of life ( QOL ) was assessed in a subgroup of patients . Data from the two trials were combined to allow multivariate and stratified survival analyses . RESULTS Seven hundred ninety-seven eligible patients were r and omized , 446 in MIC1 and 351 
    Output:
    