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: PURPOSE Combining cisplatin or cetuximab with radiation improves overall survival ( OS ) of patients with stage III or IV head and neck carcinoma ( HNC ) .  Cetuximab plus platinum regimens also increase OS in metastatic HNC . The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival ( PFS ) . PATIENTS AND METHODS Eligible patients with stage III or IV HNC were r and omly assigned to receive radiation and cisplatin without ( arm A ) or with ( arm B ) cetuximab .  Acute and late reactions were scored using Common Terminology Criteria for Adverse Events ( version 3 ) . Outcomes were correlated with patient and tumor features and markers . RESULTS Of 891 analyzed patients , 630 were alive at analysis ( median follow-up , 3.8 years ) . Cetuximab plus cisplatin-radiation , versus cisplatin-radiation alone , result ed in more frequent interruptions in radiation therapy ( 26.9 % v. 15.1 % , respectively ) ; similar cisplatin delivery ( mean , 185.7 mg/m2 v. 191.1 mg/m2 , respectively ) ; and more grade 3 to 4 radiation mucositis ( 43.2 % v. 33.3 % , respectively ) , rash , fatigue , anorexia , and hypokalemia , but not more late toxicity . No differences were found between arms A and B in 30-day mortality ( 1.8 % v. 2.0 % , respectively ; P = .81 ) , 3-year PFS ( 61.2 % v. 58.9 % , respectively ; P = .76 ) , 3-year OS ( 72.9 % v. 75.8 % , respectively ; P = .32 ) , locoregional failure ( 19.9 % v. 25.9 % , respectively ; P = .97 ) , or distant metastasis ( 13.0 % v. 9.7 % , respectively ; P = .08 ) . Patients with p16-positive oropharyngeal carcinoma ( OPC ) , compared with patients with p16-negative OPC , had better 3-year probability of PFS ( 72.8 % v. 49.2 % , respectively ; P < .001 ) and OS ( 85.6 % v. 60.1 % , respectively ; P < .001 ) , but tumor epidermal growth factor receptor ( EGFR ) expression did not distinguish outcome . CONCLUSION Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely . PFS and OS were higher in patients with p16-positive OPC , but outcomes did not differ by EGFR expression 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 BACKGROUND A r and omized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil ( TPF ) with cisplatin and fluorouracil ( PF ) , followed by chemoradiotherapy . METHODS We r and omly assigned 501 patients ( all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were c and i date s for organ preservation ) to receive either TPF or PF induction chemotherapy  , followed  by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week . The primary end point was overall survival . RESULTS With a minimum of 2 years of follow-up ( > or =3 years for 69 % of patients ) , significantly more patients survived in the TPF group than in the PF group ( hazard ratio for death , 0.70 ; P=0.006 ) . Estimates of overall survival at 3 years were 62 % in the TPF group and 48 % in the PF group ; the median overall survival was 71 months and 30 months , respectively ( P=0.006 ) . There was better locoregional control in the TPF group than in the PF group ( P=0.04 ) , but the incidence of distant metastases in the two groups did not differ significantly ( P=0.14 ) . Rates of neutropenia and febrile neutropenia were higher in the TPF group ; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group . CONCLUSIONS Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy . ( Clinical Trials.gov number , NCT00273546 [ Clinical Trials.gov ] . ) BACKGROUND Cetuximab combined with radiotherapy ( RT ) is a treatment option for head and neck cancer . The objectives of this r and omized , phase II trial were to evaluate the efficacy and safety of cetuximab maintenance therapy following definitive RT with concomitant cetuximab in patients with oropharyngeal cancer . PATIENTS AND METHODS Ninety-one patients with stage III-IV M0 oropharyngeal tumors were r and omly assigned to the treatment with accelerated concomitant boost RT ( 69.9 Gy ) + cetuximab or the same treatment with the addition of 12 consecutive weeks of cetuximab maintenance therapy . The primary end point was locoregional control ( LRC ) at 1 year . RESULTS LRC at 1 year was superior among patients in the experimental arm , treated with cetuximab maintenance ( 59 % versus 47 % ) . However , LRC was similar between both arms after 2 years of follow-up , as a result of increased locoregional recurrences after the first year in the maintenance group . Patients treated with adjuvant cetuximab do recover very soon from toxic effect after combined treatment . CONCLUSIONS Twelve weeks of cetuximab maintenance therapy after concomitant cetuximab + RT in locally advanced oropharyngeal carcinoma is feasible and improves clinical outcomes measured at 1 year . This improvement is not maintained after the second year suggesting that epidermal growth factor receptor blockade is not sufficient to completely eliminate the minimal residual disease PURPOSE The long term results and patterns of failure in patients with squamous cell head and neck carcinoma ( SCHNC ) treated in a prospect i ve r and omized trial in which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin ( CRT ) was compared with radiotherapy only ( RT ) , were analyzed . PATIENTS AND METHODS Between March 1997 and December 2001 , 114 eligible patients with Stage III or IV SCHNC were r and omized .  Primary surgical treatment was performed with curative intent in all patients . Patients in both groups were postoperatively irradiated to the total dose of 56 - 70 Gy . Chemotherapy included Mitomycin C 15 mg/m2 after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation . Median follow-up was 76 months ( 48 - 103 months ) . RESULTS At 5 years in the RT and CRT arms , the locoregional control was 65 % and 88 % ( p = 0.026 ) , disease-free survival 33 % and 53 % ( p = 0.035 ) , and overall survival 37 % and 55 % ( p = 0.091 ) respectively . Patients who benefited from chemotherapy were those with high-risk factors . The probability of distant metastases was 22 % in RT and 20 % in CRT arm ( p = 0.913 ) , of grade III or higher late toxicity 19 % in RT and 26 % in CRT arm ( p = 0.52 ) and of thyroid dysfunction 36 % in RT and 56 % in CRT arm ( p = 0.24 ) . The probability to develop a second primary malignancy ( SPM ) was 34 % in the RT and 8 % in the CRT arm ( p = 0.023 ) . One third of deaths were due to infection , but there was no difference between the 2 groups . CONCLUSION With concomitant radiochemotherapy , locoregional control and disease free survival were significantly improved . Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent . The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation PURPOSE Promising results in a r and omized phase II trial with the hypoxic cytotoxin tirapazamine ( TPZ ) combined with cisplatin ( CIS ) and radiation led to this phase III trial . PATIENTS AND METHODS Patients with previously untreated stage III or IV ( excluding T1 - 2N1 and M1 ) squamous cell carcinoma of the oral cavity , oropharynx , hypopharynx , or larynx were r and omly assigned to receive definitive radiotherapy ( 70 Gy in 7 weeks ) concurrently with either CIS ( 100 mg/m(2 ) ) on day 1 of weeks 1 , 4 , and 7 or CIS ( 75 mg/m(2 ) ) plus TPZ ( 290 mg/m(2)/d ) on day 1 of weeks 1 , 4 , and 7 and TPZ alone ( 160 mg/m(2)/d ) on days 1 , 3 , and 5 of weeks 2 and 3 ( TPZ/CIS ) . The primary end point was overall survival ( OS ) . The planned sample size was 850 , estimated to result in 334 deaths , which would provide 90 % power to detect a difference in 2-year survival rates of 60 % v 70 % for CIS versus TPZ/CIS , respectively ( hazard ratio = 0.69 ) . RESULTS Eight hundred sixty-one patients were accrued from 89 sites in 16 countries . In an intent-to-treat analysis , the 2-year OS rates were 65.7 % for CIS and 66.2 % for TPZ/CIS ( TPZ/CIS -- CIS : 95 % CI , -5.9 % to 6.9 % ) . There were no significant differences in failure-free survival , time to locoregional failure , or quality of life as measured by Functional Assessment of Cancer Therapy-Head and Neck . CONCLUSIONS We found no evidence that the addition of TPZ to chemoradiotherapy , in patients with advanced head and neck cancer not selected for the presence of hypoxia , improves OS BACKGROUND Phase 2 studies suggest that the st and ard regimen of cisplatin and fluorouracil ( PF ) plus docetaxel ( TPF ) improves outcomes in squamous-cell carcinoma of the head and neck . We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced , unresectable disease . METHODS We r and omly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF ( docetaxel and cisplatin , day 1 ; fluorouracil by continuous infusion , days 1 to 5 ) or PF every 3 weeks for four cycles . Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chem 
    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: PURPOSE Combining cisplatin or cetuximab with radiation improves overall survival ( OS ) of patients with stage III or IV head and neck carcinoma ( HNC ) .  Cetuximab plus platinum regimens also increase OS in metastatic HNC . The Radiation Therapy Oncology Group launched a phase III trial to test the hypothesis that adding cetuximab to the radiation-cisplatin platform improves progression-free survival ( PFS ) . PATIENTS AND METHODS Eligible patients with stage III or IV HNC were r and omly assigned to receive radiation and cisplatin without ( arm A ) or with ( arm B ) cetuximab .  Acute and late reactions were scored using Common Terminology Criteria for Adverse Events ( version 3 ) . Outcomes were correlated with patient and tumor features and markers . RESULTS Of 891 analyzed patients , 630 were alive at analysis ( median follow-up , 3.8 years ) . Cetuximab plus cisplatin-radiation , versus cisplatin-radiation alone , result ed in more frequent interruptions in radiation therapy ( 26.9 % v. 15.1 % , respectively ) ; similar cisplatin delivery ( mean , 185.7 mg/m2 v. 191.1 mg/m2 , respectively ) ; and more grade 3 to 4 radiation mucositis ( 43.2 % v. 33.3 % , respectively ) , rash , fatigue , anorexia , and hypokalemia , but not more late toxicity . No differences were found between arms A and B in 30-day mortality ( 1.8 % v. 2.0 % , respectively ; P = .81 ) , 3-year PFS ( 61.2 % v. 58.9 % , respectively ; P = .76 ) , 3-year OS ( 72.9 % v. 75.8 % , respectively ; P = .32 ) , locoregional failure ( 19.9 % v. 25.9 % , respectively ; P = .97 ) , or distant metastasis ( 13.0 % v. 9.7 % , respectively ; P = .08 ) . Patients with p16-positive oropharyngeal carcinoma ( OPC ) , compared with patients with p16-negative OPC , had better 3-year probability of PFS ( 72.8 % v. 49.2 % , respectively ; P < .001 ) and OS ( 85.6 % v. 60.1 % , respectively ; P < .001 ) , but tumor epidermal growth factor receptor ( EGFR ) expression did not distinguish outcome . CONCLUSION Adding cetuximab to radiation-cisplatin did not improve outcome and hence should not be prescribed routinely . PFS and OS were higher in patients with p16-positive OPC , but outcomes did not differ by EGFR expression 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 BACKGROUND A r and omized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil ( TPF ) with cisplatin and fluorouracil ( PF ) , followed by chemoradiotherapy . METHODS We r and omly assigned 501 patients ( all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were c and i date s for organ preservation ) to receive either TPF or PF induction chemotherapy  , followed  by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week . The primary end point was overall survival . RESULTS With a minimum of 2 years of follow-up ( > or =3 years for 69 % of patients ) , significantly more patients survived in the TPF group than in the PF group ( hazard ratio for death , 0.70 ; P=0.006 ) . Estimates of overall survival at 3 years were 62 % in the TPF group and 48 % in the PF group ; the median overall survival was 71 months and 30 months , respectively ( P=0.006 ) . There was better locoregional control in the TPF group than in the PF group ( P=0.04 ) , but the incidence of distant metastases in the two groups did not differ significantly ( P=0.14 ) . Rates of neutropenia and febrile neutropenia were higher in the TPF group ; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group . CONCLUSIONS Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy . ( Clinical Trials.gov number , NCT00273546 [ Clinical Trials.gov ] . ) BACKGROUND Cetuximab combined with radiotherapy ( RT ) is a treatment option for head and neck cancer . The objectives of this r and omized , phase II trial were to evaluate the efficacy and safety of cetuximab maintenance therapy following definitive RT with concomitant cetuximab in patients with oropharyngeal cancer . PATIENTS AND METHODS Ninety-one patients with stage III-IV M0 oropharyngeal tumors were r and omly assigned to the treatment with accelerated concomitant boost RT ( 69.9 Gy ) + cetuximab or the same treatment with the addition of 12 consecutive weeks of cetuximab maintenance therapy . The primary end point was locoregional control ( LRC ) at 1 year . RESULTS LRC at 1 year was superior among patients in the experimental arm , treated with cetuximab maintenance ( 59 % versus 47 % ) . However , LRC was similar between both arms after 2 years of follow-up , as a result of increased locoregional recurrences after the first year in the maintenance group . Patients treated with adjuvant cetuximab do recover very soon from toxic effect after combined treatment . CONCLUSIONS Twelve weeks of cetuximab maintenance therapy after concomitant cetuximab + RT in locally advanced oropharyngeal carcinoma is feasible and improves clinical outcomes measured at 1 year . This improvement is not maintained after the second year suggesting that epidermal growth factor receptor blockade is not sufficient to completely eliminate the minimal residual disease PURPOSE The long term results and patterns of failure in patients with squamous cell head and neck carcinoma ( SCHNC ) treated in a prospect i ve r and omized trial in which concomitant postoperative radiochemotherapy with Mitomycin C and Bleomycin ( CRT ) was compared with radiotherapy only ( RT ) , were analyzed . PATIENTS AND METHODS Between March 1997 and December 2001 , 114 eligible patients with Stage III or IV SCHNC were r and omized .  Primary surgical treatment was performed with curative intent in all patients . Patients in both groups were postoperatively irradiated to the total dose of 56 - 70 Gy . Chemotherapy included Mitomycin C 15 mg/m2 after 10 Gy and 5 mg of Bleomycin twice weekly during irradiation . Median follow-up was 76 months ( 48 - 103 months ) . RESULTS At 5 years in the RT and CRT arms , the locoregional control was 65 % and 88 % ( p = 0.026 ) , disease-free survival 33 % and 53 % ( p = 0.035 ) , and overall survival 37 % and 55 % ( p = 0.091 ) respectively . Patients who benefited from chemotherapy were those with high-risk factors . The probability of distant metastases was 22 % in RT and 20 % in CRT arm ( p = 0.913 ) , of grade III or higher late toxicity 19 % in RT and 26 % in CRT arm ( p = 0.52 ) and of thyroid dysfunction 36 % in RT and 56 % in CRT arm ( p = 0.24 ) . The probability to develop a second primary malignancy ( SPM ) was 34 % in the RT and 8 % in the CRT arm ( p = 0.023 ) . One third of deaths were due to infection , but there was no difference between the 2 groups . CONCLUSION With concomitant radiochemotherapy , locoregional control and disease free survival were significantly improved . Second primary malignancies in the CRT arm compared to RT arm were significantly less frequent . The high probability of post treatment hypothyroidism in both arms warrants regular laboratory evaluation PURPOSE Promising results in a r and omized phase II trial with the hypoxic cytotoxin tirapazamine ( TPZ ) combined with cisplatin ( CIS ) and radiation led to this phase III trial . PATIENTS AND METHODS Patients with previously untreated stage III or IV ( excluding T1 - 2N1 and M1 ) squamous cell carcinoma of the oral cavity , oropharynx , hypopharynx , or larynx were r and omly assigned to receive definitive radiotherapy ( 70 Gy in 7 weeks ) concurrently with either CIS ( 100 mg/m(2 ) ) on day 1 of weeks 1 , 4 , and 7 or CIS ( 75 mg/m(2 ) ) plus TPZ ( 290 mg/m(2)/d ) on day 1 of weeks 1 , 4 , and 7 and TPZ alone ( 160 mg/m(2)/d ) on days 1 , 3 , and 5 of weeks 2 and 3 ( TPZ/CIS ) . The primary end point was overall survival ( OS ) . The planned sample size was 850 , estimated to result in 334 deaths , which would provide 90 % power to detect a difference in 2-year survival rates of 60 % v 70 % for CIS versus TPZ/CIS , respectively ( hazard ratio = 0.69 ) . RESULTS Eight hundred sixty-one patients were accrued from 89 sites in 16 countries . In an intent-to-treat analysis , the 2-year OS rates were 65.7 % for CIS and 66.2 % for TPZ/CIS ( TPZ/CIS -- CIS : 95 % CI , -5.9 % to 6.9 % ) . There were no significant differences in failure-free survival , time to locoregional failure , or quality of life as measured by Functional Assessment of Cancer Therapy-Head and Neck . CONCLUSIONS We found no evidence that the addition of TPZ to chemoradiotherapy , in patients with advanced head and neck cancer not selected for the presence of hypoxia , improves OS BACKGROUND Phase 2 studies suggest that the st and ard regimen of cisplatin and fluorouracil ( PF ) plus docetaxel ( TPF ) improves outcomes in squamous-cell carcinoma of the head and neck . We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced , unresectable disease . METHODS We r and omly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF ( docetaxel and cisplatin , day 1 ; fluorouracil by continuous infusion , days 1 to 5 ) or PF every 3 weeks for four cycles . Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chem 
    Output:
    