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 Aim and background Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma . However , the poor therapeutic results justify the development of radiochemotherapy combinations . In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study , we undertook a prospect i ve multicentric r and omized trial . Material s and methods From November 1992 through December 1995 , a total of 164 patients were r and omized to receive radiotherapy alone ( arm I ) or combined ( arm II ) with daily low-dose carboplatin . Results The 3 , 5 and 10-year local-regional recurrence-free survival rates were better in arm II(21.7 % , 15.1 % and 15.1 % , respectively ) than in arm I ( 15 % , 10.7 % and 10.7 % ) , but without statistical significance ( P = 0.11 ) . The 3 , 5 and 10-year disease-free survival rates showed the same positive trend for arm II ( 16 % , 6.8 % and 6.8 % vs 9 % , 5.5 % and 5.5 % , in arm I , respectively ) , again without statistical significance ( P = 0.09 ) . Instead , a statistical advantage was found in overall survival rates at 3 , 5 and 10-years ( 28.9 % , 9 % and 5.5 % in arm II and 11.1 % , 6.9 % and 6.9 % in arm I , respectively ) ( P = 0.02 ) . The 3 , 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II ( 21.5 % , 15.9 % and 15.9 % ) than in arm I ( 12.8 % , 7.7 % and 7.7 % , respectively ) ( P = 0.04 ) . Conclusions Long-term results in both treatment arms of the trial appear less positive than most published series . However , our findings do not exclude that carboplatin may be beneficial , but the benefit in local control must be lower than the 15 % assumed to dimension the trial BACKGROUND Single-modality radiotherapy is still considered st and ard treatment for patients with locally advanced unresectable cancer of the head and neck . As treatment outcome is poor , attempts to integrate chemotherapy into the overall management of these patients are ongoing . PATIENTS AND METHODS A r and omized study was undertaken to compare a sequential with a simultaneous chemoradiotherapy program . Between February 1986 and February 1991 , 93 eligible patients with locally advanced unresectable cancer of the head and neck were stratified by WHO PS , T and N class and primary site and then r and omized to receive either three courses of neoadjuvant chemotherapy with cisplatin ( 100 mg/m2 i.v . d 1 ) and 5-fluorouracil 1000 mg/m2/days 1 - 5 by continuous i.v . infusion every 3 weeks prior to definitive conventional radiotherapy of 65 - 70 Gy ( sequential treatment ) , or cisplatin 100 mg/m2 on days 1 , 22 , 43 given simultaneously for the duration of the same conventional radiotherapy ( simultaneous treatment ) . RESULTS At the end of the entire treatment 18 complete responses ( 47 % ) in the sequential-treatment arm and 18 ( 41 % ) in the simultaneous treatment arm were obtained . No statistically significant differences in the 5-yr progression-free survival , in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed . Leukopenia was more frequent in the simultaneous than in the sequential arm ( p = 0.03 ) , whereas alopecia ( p = 0.008 ) and phlebitis ( p < 0.0001 ) were more frequent in the sequential-treatment arm . A better compliance was associated with the concomitant treatment , with 87 % of the patients completing the entire radiotherapy program versus 63 % of those in the sequential arm ( p = 0.01 ) . CONCLUSIONS In the present study , the two treatment arms showed similar activity ( complete response , progression-free and overall survival rates ) . Compliance to treatment was better in the concomitant arm . These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck . Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone The r and omization of 155 patients with advanced head and neck carcinomas into 5 subgroups related to the site of origin result ed in 2 comparable groups suitable for study . One group was treated with external radiation alone , the second group was treated with external radiation plus concomitant systemic 5-FU . The improved cure rate and average survival of the entire group was statistically significant ; however , the tabulated results indicated that the better results in the combination treated group were present in the lesions originating in the oral cavity or oropharynx . All of these lesions were squamous cell carcinomas . The 106 lesions which were r and omized in these 2 areas demonstrated an impressive advantage for the combination therapy .  Reactions to therapy with the combination group are slightly more severe but are certainly within tolerable limits . We have not demonstrated a greater long-term number of complications . The results of the study indicate a need for a similar cooperative study in an effort t Between January 1996 and November 1998 38 patients were treated with induction chemotherapy .  Patients were distributed in two r and omized groups , 19 - 19 patients in each , receiving ( group N ) either bleomycin , vincristine and methotrexate ( BVM ) or the previous medication plus cisplatin ( BVCM ) chemotherapy ( group C ) . Side effects were low and reversible during the treatments . The clinical regression rate ( RR ) of the cases was 87 % including complete regression 24 % . There was no difference between the two groups . There was no difference in the pathological macroscopic regression , however group C was better in microscopic regression . During the 27.5 months of average follow-up time , group N had a significantly better result in the tumor-free survival , with a lower rate of metastatic recidives ( N/C = 2/9 ) . There was no significant difference in the overall survival rate , due to the radical neck dissections of recidive metastases . According to our experience we recommend the use of cisplatin in conjunction with neck radiotherapy In a r and omized double-blind trial hydroxyurea was compared to placebo in conjunction with radiotherapy of head and neck cancer .  Chemotherapy was given orally twice a week ( 80 mg∕kg ) concurrently with irradiation . Comparison of the 2 groups for primary tumor regression , cervical node response , and early survival fails to show statistically significant differences . Combined treatment may be useful in massive node metastases . Increased local radiation reactions were frequent in the hydroxyurea group and severe with interstitial implants . The drug was generally well tolerated . Complications of treatment and an apparently higher incidence of distant metastases are discussed Two hundred and forty-one patients , with advanced squamous cell carcinoma of head and neck , were r and omized to receive three courses of  induction chemotherapy . The chemotherapy regimens were delivered every 3 weeks , and consisted in 1 ) cisplatin , 80 mg/m2 given alone ( CDDP regimen ) , or 2 ) in combination with vincristine , 1 mg , d 1 , methotrexate 10 mg/m2 d 1 , 2 , 3 , and bleomycin 10 mg/m2 , d 1 , 2 , and 3 ( MOB-P ) . Tolerance was significantly better with the CDDP regimen ( p less than 0.05 ) ; severe side effects , affecting mainly digestive tract , and bone marrow , were encountered in 7 % of the patients in the CDDP group , vs 15 % in the MOB-P group , without death related to pancytopenia . Short-term results were better for patients treated by the MOB-P regimen , with a 42 % response rate ( including 9 complete responses ) vs 22 % with the CDDP regimen ( p = 0.01 ) . A superiority of combination chemotherapy was more significant for primary sites than regional lymph nodes . The relapse-free survival was not statistically different in the 2 groups , as well as the 2 years overall survival . Among responders , the survival was found highly correlated with a good initial general status ( p less than 0.01 ) , and with the highest total doses of cisplatin ( p less than 0.02 ) . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma ( SCC ) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial . PATIENTS AND METHODS One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were r and omized to receive definitive radiotherapy ( 70 Gy in 7 weeks ) concurrently with either cisplatin ( 75 mg/m(2 ) ) plus tirapazamine ( 290 mg/m(2)/d ) on day 2 of weeks 1 , 4 , and 7 , and tirapazamine alone ( 160 mg/m(2)/d ) on days 1 , 3 , and 5 of weeks 2 and 3 ( TPZ/CIS ) , or cisplatin ( 50 mg/m(2 ) ) on day 1 and infusional fluorouracil ( 360 mg/m(2)/d ) on days 1 through 5 of weeks 6 and 7 ( chemoboost ) . RESULTS Three-year failure-free survival rates were 55 % with TPZ/CIS ( 95 % CI , 39 % to 70 % ) and 44 % with chemoboost ( 95 % CI , 30 % to 60 % ; log-rank P = .16 ) . Three-year locoregional failure-free rates were 84 % in the TPZ/CIS arm ( 95 % CI , 71 % to 92 % ) and 66 % in the chemoboost arm ( 95 % CI , 51 % to 79 % ; P = .069 ) . More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS , while acute skin radiation reaction was more severe and prolonged with chemoboost . Compliance with protocol treatment was satisfactory on both arms . CONCLUSION Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting . Based on the promising efficacy seen in this trial , TPZ/CIS is being evaluated in a large phase III trial PURPOSE To exp and on our experience with the combination of paclitaxel , fluorouracil , hydroxyurea , and twice daily irradiation ( T-FHX ) and to assess the impact of weekly administration of erythropoietin ( r-HuEpo ) on transfusion requirements , we conducted a Phase II multi-institutional trial with a simplified 1-h paclitaxel infusion schedule and r and omized patients to receive weekly doses of r-HuEpo . PATIENTS AND METHODS A total of 90 patients with locally advanced head and neck cancers ( stage IV , 96 % ; N(2)/N(3 ) , 66 % ) were treated on a regimen of 1-h infusion of paclitaxel ( 100 mg/m(2)/ 
    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: 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 Aim and background Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma . However , the poor therapeutic results justify the development of radiochemotherapy combinations . In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study , we undertook a prospect i ve multicentric r and omized trial . Material s and methods From November 1992 through December 1995 , a total of 164 patients were r and omized to receive radiotherapy alone ( arm I ) or combined ( arm II ) with daily low-dose carboplatin . Results The 3 , 5 and 10-year local-regional recurrence-free survival rates were better in arm II(21.7 % , 15.1 % and 15.1 % , respectively ) than in arm I ( 15 % , 10.7 % and 10.7 % ) , but without statistical significance ( P = 0.11 ) . The 3 , 5 and 10-year disease-free survival rates showed the same positive trend for arm II ( 16 % , 6.8 % and 6.8 % vs 9 % , 5.5 % and 5.5 % , in arm I , respectively ) , again without statistical significance ( P = 0.09 ) . Instead , a statistical advantage was found in overall survival rates at 3 , 5 and 10-years ( 28.9 % , 9 % and 5.5 % in arm II and 11.1 % , 6.9 % and 6.9 % in arm I , respectively ) ( P = 0.02 ) . The 3 , 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II ( 21.5 % , 15.9 % and 15.9 % ) than in arm I ( 12.8 % , 7.7 % and 7.7 % , respectively ) ( P = 0.04 ) . Conclusions Long-term results in both treatment arms of the trial appear less positive than most published series . However , our findings do not exclude that carboplatin may be beneficial , but the benefit in local control must be lower than the 15 % assumed to dimension the trial BACKGROUND Single-modality radiotherapy is still considered st and ard treatment for patients with locally advanced unresectable cancer of the head and neck . As treatment outcome is poor , attempts to integrate chemotherapy into the overall management of these patients are ongoing . PATIENTS AND METHODS A r and omized study was undertaken to compare a sequential with a simultaneous chemoradiotherapy program . Between February 1986 and February 1991 , 93 eligible patients with locally advanced unresectable cancer of the head and neck were stratified by WHO PS , T and N class and primary site and then r and omized to receive either three courses of neoadjuvant chemotherapy with cisplatin ( 100 mg/m2 i.v . d 1 ) and 5-fluorouracil 1000 mg/m2/days 1 - 5 by continuous i.v . infusion every 3 weeks prior to definitive conventional radiotherapy of 65 - 70 Gy ( sequential treatment ) , or cisplatin 100 mg/m2 on days 1 , 22 , 43 given simultaneously for the duration of the same conventional radiotherapy ( simultaneous treatment ) . RESULTS At the end of the entire treatment 18 complete responses ( 47 % ) in the sequential-treatment arm and 18 ( 41 % ) in the simultaneous treatment arm were obtained . No statistically significant differences in the 5-yr progression-free survival , in the median time to loco-regional and distant progression and in the 5-yr overall survival were observed . Leukopenia was more frequent in the simultaneous than in the sequential arm ( p = 0.03 ) , whereas alopecia ( p = 0.008 ) and phlebitis ( p < 0.0001 ) were more frequent in the sequential-treatment arm . A better compliance was associated with the concomitant treatment , with 87 % of the patients completing the entire radiotherapy program versus 63 % of those in the sequential arm ( p = 0.01 ) . CONCLUSIONS In the present study , the two treatment arms showed similar activity ( complete response , progression-free and overall survival rates ) . Compliance to treatment was better in the concomitant arm . These data suggest that concomitant chemo-radiation therapy might be considered an option in unresectable locally advanced cancer of the head and neck . Phase III studies are needed in order to establish the superiority of this combination of cisplatin and radiotherapy versus radiotherapy alone The r and omization of 155 patients with advanced head and neck carcinomas into 5 subgroups related to the site of origin result ed in 2 comparable groups suitable for study . One group was treated with external radiation alone , the second group was treated with external radiation plus concomitant systemic 5-FU . The improved cure rate and average survival of the entire group was statistically significant ; however , the tabulated results indicated that the better results in the combination treated group were present in the lesions originating in the oral cavity or oropharynx . All of these lesions were squamous cell carcinomas . The 106 lesions which were r and omized in these 2 areas demonstrated an impressive advantage for the combination therapy .  Reactions to therapy with the combination group are slightly more severe but are certainly within tolerable limits . We have not demonstrated a greater long-term number of complications . The results of the study indicate a need for a similar cooperative study in an effort t Between January 1996 and November 1998 38 patients were treated with induction chemotherapy .  Patients were distributed in two r and omized groups , 19 - 19 patients in each , receiving ( group N ) either bleomycin , vincristine and methotrexate ( BVM ) or the previous medication plus cisplatin ( BVCM ) chemotherapy ( group C ) . Side effects were low and reversible during the treatments . The clinical regression rate ( RR ) of the cases was 87 % including complete regression 24 % . There was no difference between the two groups . There was no difference in the pathological macroscopic regression , however group C was better in microscopic regression . During the 27.5 months of average follow-up time , group N had a significantly better result in the tumor-free survival , with a lower rate of metastatic recidives ( N/C = 2/9 ) . There was no significant difference in the overall survival rate , due to the radical neck dissections of recidive metastases . According to our experience we recommend the use of cisplatin in conjunction with neck radiotherapy In a r and omized double-blind trial hydroxyurea was compared to placebo in conjunction with radiotherapy of head and neck cancer .  Chemotherapy was given orally twice a week ( 80 mg∕kg ) concurrently with irradiation . Comparison of the 2 groups for primary tumor regression , cervical node response , and early survival fails to show statistically significant differences . Combined treatment may be useful in massive node metastases . Increased local radiation reactions were frequent in the hydroxyurea group and severe with interstitial implants . The drug was generally well tolerated . Complications of treatment and an apparently higher incidence of distant metastases are discussed Two hundred and forty-one patients , with advanced squamous cell carcinoma of head and neck , were r and omized to receive three courses of  induction chemotherapy . The chemotherapy regimens were delivered every 3 weeks , and consisted in 1 ) cisplatin , 80 mg/m2 given alone ( CDDP regimen ) , or 2 ) in combination with vincristine , 1 mg , d 1 , methotrexate 10 mg/m2 d 1 , 2 , 3 , and bleomycin 10 mg/m2 , d 1 , 2 , and 3 ( MOB-P ) . Tolerance was significantly better with the CDDP regimen ( p less than 0.05 ) ; severe side effects , affecting mainly digestive tract , and bone marrow , were encountered in 7 % of the patients in the CDDP group , vs 15 % in the MOB-P group , without death related to pancytopenia . Short-term results were better for patients treated by the MOB-P regimen , with a 42 % response rate ( including 9 complete responses ) vs 22 % with the CDDP regimen ( p = 0.01 ) . A superiority of combination chemotherapy was more significant for primary sites than regional lymph nodes . The relapse-free survival was not statistically different in the 2 groups , as well as the 2 years overall survival . Among responders , the survival was found highly correlated with a good initial general status ( p less than 0.01 ) , and with the highest total doses of cisplatin ( p less than 0.02 ) . ( ABSTRACT TRUNCATED AT 250 WORDS PURPOSE To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma ( SCC ) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group phase III trial . PATIENTS AND METHODS One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were r and omized to receive definitive radiotherapy ( 70 Gy in 7 weeks ) concurrently with either cisplatin ( 75 mg/m(2 ) ) plus tirapazamine ( 290 mg/m(2)/d ) on day 2 of weeks 1 , 4 , and 7 , and tirapazamine alone ( 160 mg/m(2)/d ) on days 1 , 3 , and 5 of weeks 2 and 3 ( TPZ/CIS ) , or cisplatin ( 50 mg/m(2 ) ) on day 1 and infusional fluorouracil ( 360 mg/m(2)/d ) on days 1 through 5 of weeks 6 and 7 ( chemoboost ) . RESULTS Three-year failure-free survival rates were 55 % with TPZ/CIS ( 95 % CI , 39 % to 70 % ) and 44 % with chemoboost ( 95 % CI , 30 % to 60 % ; log-rank P = .16 ) . Three-year locoregional failure-free rates were 84 % in the TPZ/CIS arm ( 95 % CI , 71 % to 92 % ) and 66 % in the chemoboost arm ( 95 % CI , 51 % to 79 % ; P = .069 ) . More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS , while acute skin radiation reaction was more severe and prolonged with chemoboost . Compliance with protocol treatment was satisfactory on both arms . CONCLUSION Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting . Based on the promising efficacy seen in this trial , TPZ/CIS is being evaluated in a large phase III trial PURPOSE To exp and on our experience with the combination of paclitaxel , fluorouracil , hydroxyurea , and twice daily irradiation ( T-FHX ) and to assess the impact of weekly administration of erythropoietin ( r-HuEpo ) on transfusion requirements , we conducted a Phase II multi-institutional trial with a simplified 1-h paclitaxel infusion schedule and r and omized patients to receive weekly doses of r-HuEpo . PATIENTS AND METHODS A total of 90 patients with locally advanced head and neck cancers ( stage IV , 96 % ; N(2)/N(3 ) , 66 % ) were treated on a regimen of 1-h infusion of paclitaxel ( 100 mg/m(2)/ 
    Output:
    