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 Background We investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck . Methods Patients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab ( 400 mg/m2 initial dose then 250 mg/m2 weekly ) for 7 weeks plus concomitant boost radiotherapy ( weeks 2–7 : once daily [ 1.8 Gy ] for 3.6 weeks , then twice daily [ 1.8 Gy morning and 1.5 Gy afternoon ] for 2.4 weeks ) . The primary endpoint was treatment completion rate ( the rate of treated patients completing ≥70 % of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule ) . Results Twenty-two patients were evaluable . The treatment completion rate was 100 % ( 95 % confidence interval 85–100 ) . The response rate 8 weeks post-radiotherapy was 82 % ( 95 % confidence interval 60–95 ) . The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation ( 73 % ) ; dermatitis ( 27 % ) ; and infection , radiation skin injury and stomatitis ( 23 % each ) . Conclusions Cetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck . Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck 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 BACKGROUND We studied the combination of pemetrexed , a multi-targeted antifolate , and cetuximab , an mAb against the epidermal growth factor receptor , with radiotherapy in poor prognosis head and neck cancer . PATIENTS AND METHODS Patients received pemetrexed on days 1 , 22 , and 43 on a dose-escalation scheme with starting level ( 0 ) 350 mg/m(2 ) ( level -1 , 200 mg/m(2 ) ; level + 1 , 500 mg/m(2 ) ) with concurrent radiotherapy ( 2 Gy/day ) and cetuximab in two separate cohorts , not previously irradiated ( A ) and previously irradiated ( B ) , who received 70 and 60 - 66 Gy , respectively . Genetic polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase were evaluated . RESULTS Thirty-two patients were enrolled . The maximum tolerated dose of pemetrexed was 500 mg/m(2 ) in cohort A and 350 mg/m(2 ) in cohort B. Prophylactic antibiotics were required . In cohort A , two dose-limiting toxicities ( DLTs ) occurred ( febrile neutropenia ) , one each at levels 0 and + 1 . In cohort B , two DLTs occurred at level + 1 ( febrile neutropenia ; death from perforated duodenal ulcer and sepsis ) . Grade 3 mucositis was common . No association of gene polymorphisms with toxicity or efficacy was evident . CONCLUSION The addition of pemetrexed 500 mg/m(2 ) to cetuximab and radiotherapy is recommended for further study in not previously irradiated patients BACKGROUND Intensification of chemoradiation for advanced head and neck squamous cell carcinoma ( HNSCC ) is unlikely due to toxicity . Cetuximab combined either with radiotherapy or with chemotherapy showed favourable toxic profile with positive results in both combinations . Therefore , cetuximab could intensify chemoradiation without worsening toxicity . We conducted a phase II study of chemoradiation and cetuximab . PATIENTS AND METHODS Eligible patients had stage III-IV M0 HNSCC . Treatment consisted of three cycles of cisplatin ( 20 mg/m(2)/day × 5 days ) and fluorouracil ( 200 mg/m(2)/day × 5 days ) rapidly alternated to three split courses of radiotherapy up to 70 Gy and concurrent weekly cetuximab . The primary end point of the study was complete response ( CR ) rate . Secondary end points were toxicity , progression-free survival ( PFS ) and overall survival ( OS ) . RESULTS Fourty-five patients were enrolled : median age was 56 years , 38 had stage IV disease and 40 nodal involvement .  CR occurred in 32 patients ( 71 % ) . PFS and OS was 21 + months and 32.6 + , respectively . Acute grade 3 - 4 toxic effects were in the expected range , but grade 3 radiodermatitis occurred in 33 patients . CONCLUSIONS The combination of cetuximab , cisplatin , fluorouracil and radiotherapy leads to a very high proportion of CR and it is feasible with toxic effects similar to those expected by radiochemotherapy . The only unexpected toxicity was skin toxicity : grade 3 radiodermatitis occurred in 73 % of the patients BACKGROUND E2303 evaluated cetuximab , paclitaxel , and carboplatin used as induction therapy and concomitant with radiation therapy in patients with stage III/IV head and neck squamous cell carcinoma ( HNSCC ) determining pathologic complete response ( CR ) , event-free survival ( EFS ) , and toxicity . PATIENTS AND METHODS Patients with resectable stage III/IV HNSCC underwent induction therapy with planned primary site restaging biopsies ( at week 8 in clinical complete responders and at week 14 if disease persisted ) . Chemoradiation ( CRT ) began week 9 . If week 14 biopsy was negative , patients completed CRT ( 68 - 72 Gy ) ; otherwise , resection was carried out . p16 protein expression status was correlated with response/survival . RESULTS Seventy-four patients were enrolled ; 63 were eligible . Forty-four ( 70 % ) were free of surgery to the primary site , progression , and death 1-year post-treatment . Following induction , 41 ( 23 CR ) underwent week 8 primary site biopsy and 24 ( 59 % ) had no tumor ( pathologic CR ) . Week 14 biopsy during chemoradiation ( 50 Gy ) in 34 ( 15 previously positive biopsy ; 19 no prior biopsy ) was negative in 33 . Thus 90 % of eligible patients completed CRT . Overall survival and EFS were 78 % and 55 % at 3 years , respectively . Disease progression in 23 patients ( 37 % ) was local only in 10 ( 16 % ) , regional in 5 ( 8 % ) , local and regional in 2 ( 3 % ) , and distant in 5 patients ( 8 % ) . There were no treatment-related deaths . Toxicity was primarily hematologic or radiation-related . p16 AQUA score was not associated with response/survival . CONCLUSIONS Induction cetuximab , paclitaxel , and carboplatin followed by the same drug CRT is safe and induces high primary site response and promising survival . CLINICAL TRIALS NUMBER NCT 00089297 BACKGROUND To evaluate the clinical efficacies and toxicities of induction chemotherapy followed by concomitant cisplatin-chemoradiotherapy ( CRT ) or cetuximab-radiotherapy ( ERT ) in locally advanced nasopharyngeal carcinoma ( NPC ) . METHODS Previously untreated patients with stage III-IVb NPC were eligible . They were r and omized to CRT arm : intensity modulated radiation therapy ( IMRT ) with weekly cisplatin ( 30 mg/m(2)/w ) or ERT arm : IMRT with weekly cetuximab ( loading dose of 400 mg/m(2 ) followed by weekly doses of 250 mg/m(2 ) ) . Two cycles of induction chemotherapy ( docetaxel 75 mg/m(2 ) d1 and cisplatin 80 mg/m(2 ) d1 ) were administered to both arms . Endpoints were survivals , toxicities and quality of life ( QoL ) . RESULTS Because of the unexpectedly high rates of grade 3/4 mucositis observed in the ERT arm , the study was closed ahead of schedule . A total of 44 patients ( 23 in CRT arm and 21 in ERT arm ) were enrolled . All patients completed the scheduled induction chemotherapy and radical radiotherapy . The results showed better compliance ( P<0.001 ) with more oral mucositis , acneiform rash and dysphagia ( P<0.05 ) of cetuximab . The 3-year disease-free survival ( DFS ) were achieved as 78.3 % and 85.7 % ( P=0.547 ) in CRT and ERT arm , respectively . In the analysis of QoL , the addition of cetuximab to radiotherapy temporarily increased the adverse symptoms but did not result in long-term dysfunction . CONCLUSIONS ERT was not more efficacious than CRT but was more likely to cause acute adverse events in LA NPC . The recommended treatment modality was still concurrent cisplatin- 
    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 Background We investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck . Methods Patients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab ( 400 mg/m2 initial dose then 250 mg/m2 weekly ) for 7 weeks plus concomitant boost radiotherapy ( weeks 2–7 : once daily [ 1.8 Gy ] for 3.6 weeks , then twice daily [ 1.8 Gy morning and 1.5 Gy afternoon ] for 2.4 weeks ) . The primary endpoint was treatment completion rate ( the rate of treated patients completing ≥70 % of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule ) . Results Twenty-two patients were evaluable . The treatment completion rate was 100 % ( 95 % confidence interval 85–100 ) . The response rate 8 weeks post-radiotherapy was 82 % ( 95 % confidence interval 60–95 ) . The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation ( 73 % ) ; dermatitis ( 27 % ) ; and infection , radiation skin injury and stomatitis ( 23 % each ) . Conclusions Cetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck . Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck 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 BACKGROUND We studied the combination of pemetrexed , a multi-targeted antifolate , and cetuximab , an mAb against the epidermal growth factor receptor , with radiotherapy in poor prognosis head and neck cancer . PATIENTS AND METHODS Patients received pemetrexed on days 1 , 22 , and 43 on a dose-escalation scheme with starting level ( 0 ) 350 mg/m(2 ) ( level -1 , 200 mg/m(2 ) ; level + 1 , 500 mg/m(2 ) ) with concurrent radiotherapy ( 2 Gy/day ) and cetuximab in two separate cohorts , not previously irradiated ( A ) and previously irradiated ( B ) , who received 70 and 60 - 66 Gy , respectively . Genetic polymorphisms of thymidylate synthase and methylenetetrahydrofolate reductase were evaluated . RESULTS Thirty-two patients were enrolled . The maximum tolerated dose of pemetrexed was 500 mg/m(2 ) in cohort A and 350 mg/m(2 ) in cohort B. Prophylactic antibiotics were required . In cohort A , two dose-limiting toxicities ( DLTs ) occurred ( febrile neutropenia ) , one each at levels 0 and + 1 . In cohort B , two DLTs occurred at level + 1 ( febrile neutropenia ; death from perforated duodenal ulcer and sepsis ) . Grade 3 mucositis was common . No association of gene polymorphisms with toxicity or efficacy was evident . CONCLUSION The addition of pemetrexed 500 mg/m(2 ) to cetuximab and radiotherapy is recommended for further study in not previously irradiated patients BACKGROUND Intensification of chemoradiation for advanced head and neck squamous cell carcinoma ( HNSCC ) is unlikely due to toxicity . Cetuximab combined either with radiotherapy or with chemotherapy showed favourable toxic profile with positive results in both combinations . Therefore , cetuximab could intensify chemoradiation without worsening toxicity . We conducted a phase II study of chemoradiation and cetuximab . PATIENTS AND METHODS Eligible patients had stage III-IV M0 HNSCC . Treatment consisted of three cycles of cisplatin ( 20 mg/m(2)/day × 5 days ) and fluorouracil ( 200 mg/m(2)/day × 5 days ) rapidly alternated to three split courses of radiotherapy up to 70 Gy and concurrent weekly cetuximab . The primary end point of the study was complete response ( CR ) rate . Secondary end points were toxicity , progression-free survival ( PFS ) and overall survival ( OS ) . RESULTS Fourty-five patients were enrolled : median age was 56 years , 38 had stage IV disease and 40 nodal involvement .  CR occurred in 32 patients ( 71 % ) . PFS and OS was 21 + months and 32.6 + , respectively . Acute grade 3 - 4 toxic effects were in the expected range , but grade 3 radiodermatitis occurred in 33 patients . CONCLUSIONS The combination of cetuximab , cisplatin , fluorouracil and radiotherapy leads to a very high proportion of CR and it is feasible with toxic effects similar to those expected by radiochemotherapy . The only unexpected toxicity was skin toxicity : grade 3 radiodermatitis occurred in 73 % of the patients BACKGROUND E2303 evaluated cetuximab , paclitaxel , and carboplatin used as induction therapy and concomitant with radiation therapy in patients with stage III/IV head and neck squamous cell carcinoma ( HNSCC ) determining pathologic complete response ( CR ) , event-free survival ( EFS ) , and toxicity . PATIENTS AND METHODS Patients with resectable stage III/IV HNSCC underwent induction therapy with planned primary site restaging biopsies ( at week 8 in clinical complete responders and at week 14 if disease persisted ) . Chemoradiation ( CRT ) began week 9 . If week 14 biopsy was negative , patients completed CRT ( 68 - 72 Gy ) ; otherwise , resection was carried out . p16 protein expression status was correlated with response/survival . RESULTS Seventy-four patients were enrolled ; 63 were eligible . Forty-four ( 70 % ) were free of surgery to the primary site , progression , and death 1-year post-treatment . Following induction , 41 ( 23 CR ) underwent week 8 primary site biopsy and 24 ( 59 % ) had no tumor ( pathologic CR ) . Week 14 biopsy during chemoradiation ( 50 Gy ) in 34 ( 15 previously positive biopsy ; 19 no prior biopsy ) was negative in 33 . Thus 90 % of eligible patients completed CRT . Overall survival and EFS were 78 % and 55 % at 3 years , respectively . Disease progression in 23 patients ( 37 % ) was local only in 10 ( 16 % ) , regional in 5 ( 8 % ) , local and regional in 2 ( 3 % ) , and distant in 5 patients ( 8 % ) . There were no treatment-related deaths . Toxicity was primarily hematologic or radiation-related . p16 AQUA score was not associated with response/survival . CONCLUSIONS Induction cetuximab , paclitaxel , and carboplatin followed by the same drug CRT is safe and induces high primary site response and promising survival . CLINICAL TRIALS NUMBER NCT 00089297 BACKGROUND To evaluate the clinical efficacies and toxicities of induction chemotherapy followed by concomitant cisplatin-chemoradiotherapy ( CRT ) or cetuximab-radiotherapy ( ERT ) in locally advanced nasopharyngeal carcinoma ( NPC ) . METHODS Previously untreated patients with stage III-IVb NPC were eligible . They were r and omized to CRT arm : intensity modulated radiation therapy ( IMRT ) with weekly cisplatin ( 30 mg/m(2)/w ) or ERT arm : IMRT with weekly cetuximab ( loading dose of 400 mg/m(2 ) followed by weekly doses of 250 mg/m(2 ) ) . Two cycles of induction chemotherapy ( docetaxel 75 mg/m(2 ) d1 and cisplatin 80 mg/m(2 ) d1 ) were administered to both arms . Endpoints were survivals , toxicities and quality of life ( QoL ) . RESULTS Because of the unexpectedly high rates of grade 3/4 mucositis observed in the ERT arm , the study was closed ahead of schedule . A total of 44 patients ( 23 in CRT arm and 21 in ERT arm ) were enrolled . All patients completed the scheduled induction chemotherapy and radical radiotherapy . The results showed better compliance ( P<0.001 ) with more oral mucositis , acneiform rash and dysphagia ( P<0.05 ) of cetuximab . The 3-year disease-free survival ( DFS ) were achieved as 78.3 % and 85.7 % ( P=0.547 ) in CRT and ERT arm , respectively . In the analysis of QoL , the addition of cetuximab to radiotherapy temporarily increased the adverse symptoms but did not result in long-term dysfunction . CONCLUSIONS ERT was not more efficacious than CRT but was more likely to cause acute adverse events in LA NPC . The recommended treatment modality was still concurrent cisplatin- 
    Output:
    