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: We report the results of a r and omised phase II trial of docetaxel tested as a single agent in patients with recurrent head and neck cancer using methotrexate as a control arm to vali date the results . Eligibility criteria included : histologically-confirmed squamous cell carcinoma , measurable disease , adequate haematological , renal and hepatic functions , no prior chemotherapy for recurrent cancer , signed informed consent . 40 mg/m2 methotrexate was given as a short weekly bolus i.v . injection , and 40 mg/m2 docetaxel was administered as a one hour weekly infusion . A total of 57 patients were r and omised based on a ratio of 2/1:37 and 20 patients received docetaxel and methotrexate  , respectively . Patient characteristics included 49 males and 8 females ; the median age was 59 years ( range : 43 - 82 years ) . Twenty-eight patients had a local-regional relapse and 29 had distant metastasis , the median disease-free interval was 7.9 months ( range : 0 - 165 months ) . For patients treated with docetaxel , the following grade 3 - 4 toxicities occurred : neutropenia ( 12.5 % ) with febrile neutropenia in one patient ( 1 % ) , anaemia ( 19 % ) mucositis ( 9 % ) and ungueal toxicity ( 9 % ) . In the methotrexate arm , the grade 3 - 4 toxicities were : anaemia ( 15 % ) and mucositis ( 5 % ) . The response rate was significantly higher in the docetaxel arm with 27 % ( 95 % confidence interval ( CI ) : 21.7 - 32.3 % ) of objective responses versus 15 % ( 95 % CI : 11.2 - 18.8 % ) in the methotrexate arm . Overall survival and time to progression were super-imposable between the docetaxel and methotrexate treatments . Docetaxel given as a weekly infusion has a high activity in patients with head and neck cancer . A phase III trial is needed to test if this translates into a survival benefit for docetaxel use A prospect i ve r and omized study was conducted to determine the relative effectiveness , toxicity and tolerance of methotrexate ( MTX ) versus cisplatin ( DDP ) in patients with recurrent head and neck squamous cell carcinoma . Forty‐four patients were r and omized to receive either MTX , 40 mg escalated to 60 mg/m2 IV push weekly , or DDP , 50 mg/m2 6 hour infusion days 1 and 8 every 4 weeks . All patients had objective ly measurable disease and a performance status greater than 60 % ( Karnofsky scale ) . All had been treated with surgery and /or radiotherapy . No patients had prior chemotherapy . Prior treatment , performance status , and site of primary disease were comparable in both groups . Complete and partial objective responses were achieved in 23.5 % of the MTX group and 28.6 % of the DDP group ( P = 0.51 ) . Median duration of response was 84 days in the MTX group and 92 days in the DDP  group . Median survival of patients was 6.1 months with MTX and 6.3 months with DDP  . Mucositis was noted in 38 % of patients in the MTX group ( P = 0.001 ) compared to none in the DDP group . Vomiting occurred in 87 % of patients in the DDP group ( P < .0001 ) compared to 10 % of patients in the MTX group . This study demonstrates that in the treatment of recurrent head and neck squamous cell carcinoma , MTX and DDP are equally effective , although MTX appears to be better tolerated . Cancer 52:206‐210 , 1983 Thirty-eight patients with advanced , inoperable squamous cell carcinoma of the head and neck were r and omized to receive methotrexate alone or methotrexate with Bacillus Calmette-Guérin . The response rates with methotrexate ( 3 of 19 ) and methotrexate plus B. Calmette-Guérin ( 4 of 16 ) were similar , as was the duration of response and survival of the two groups . The results of in vitro immunological studies of lymphocytes were assessed . Marked weight loss , poor performance status , and distant metastases were the most important prognostic factors . The presence of anergy was significantly correlated with weight loss . This study also indicated that a large tumor burden is a frequent occurrence in advanced head and neck cancer and may account for the lack of efficacy of B. Calmette-Guérin One hundred eligible patients with inoperable , locally advanced or metastatic squamous cell carcinoma of the head and neck region following prior therapy were r and omized to receive i m methotrexate ( 50 patients ) or iv cisplatin ( 50 patients ) . Methotrexate produced a complete plus partial response rate of 16.0 % and cisplatin produced a partial response rate of 8.0 % , with median duration s of response of 18 and 8 weeks , respectively . The corresponding median survival times were 20 and 18 weeks . Methotrexate responders survived 60 weeks , versus 17 weeks for nonresponders . The corresponding survival times for cisplatin-treated patients were 38 and 18 weeks . Good pretreatment performance status had a significantly positive effect on survival ( P = 0.04 ) , but prior therapy did not . Toxicity secondary to either agent occurred with the expected frequency . The two agents examined showed comparable antitumor activity in patients with squamous cell carcinoma of the head and neck who had not previously received chemotherapy One hundred ninety‐one patients with recurrent or metastatic squamous cell carcinoma of head and neck origin were allocated at r and om to chemotherapy with conventional‐dose weekly intravenous methotrexate or the combination of cisplatin , vinblastine , and bleomycin . Methotrexate induced responses in 16 of 98 patients ( 16 % ) , whereas 22 of 92 ( 24 % ) responded to the combination regimen ( P = not significant ) . Remission duration ( 20.2 weeks methotrexate ; 15.1 weeks combination ) was similar on both arms , as was survival ( 31.4 weeks methotrexate ; 29.0 weeks combination ) . Therapy was relatively well‐tolerated on both treatment arms , although methotrexate  produced more mucositis and the combination more gastrointestinal and renal toxicity . Response to chemotherapy and disease confined to the locoregional area were associated with somewhat longer survival . Combination chemotherapy as given in this study did not improve any observed parameter , and the results of treatment were poor in both arms A prospect i ve r and omized trial was conducted at Wayne State University , Detroit , Michigan , to compare the efficacy of the combination of high‐dose cis‐diamminodichloroplatinum , Oncovin ( vincristine ) and bleomycin ( COB ) to that of weekly methotrexate ( MTX ) in the induction and maintenance of remission in patients with previously treated advanced squamous cell carcinoma of the head and neck .  Complete response ( CR ) was observed in 11.1 % of patients treated with COB and in 8.3 % of patients treated with weekly methotrexate . The overall response rate ( PR + CR ) was 33.3 % to methotrexate versus 40.7 % to COB . This difference was not significant , nor was the survival of patients treated by either modality . Important variables affecting survival in this study proved to be good performance status ( ⩾70 ) and response to therapy . Nausea and vomiting were the more common side effects of COB ( 56 % ) , while hematologic toxicity was more frequent and more severe in the methotrexate arm ( 75 % ) . Combination chemotherapy with COB is not more effective in producing response or prolonging survival than weekly methotrexate in patients with advanced head and neck carcinoma when both regimens are compared in a r and omized study Summary A phase III 2x2 factorial trial of cisplatinum and bleomycin in 116 patients with recurrent or advanced squamous cell carcinoma of the head and neck is reported . Thirty percent of patients proved to be unfit for chemotherapy , and of those treated progression of tumour was the commonest “ response ” . However , 25 % of patients achieved a partial or complete response , with no significant difference in response rates between the treated arms . The median number of courses received was 1 ( range 0–6 ) and the commonest causes for discontinuation of treatment were renal toxicity and death .  Bleomycin  reduced survival , but not significantly so , whereas cisplatinum  prolonged median survival significantly by 10 weeks . Significant predictors of survival , in addition to treatment by cisplatinum , were age , performance status , N status , number of courses and response of the tumor BACKGROUND The purpose of this study was to carry out two r and omised phase II trials of S16020 , a new olivacine derivative , tested as a single agent in patients with recurrent head and neck cancer , using methotrexate as the control arm to vali date the results . PATIENTS AND METHODS S16020 at either 80 or 100 mg/m2 was administered as a 3-h infusion every 3 weeks . Methotrexate , 40 or 50 mg/m2 , was given by bolus injection , weekly for a minimum of 6 weeks . In total , 36 patients were entered in the r and omised studies ( 25 in an initial study , 11 in a confirmatory study ) of whom 24 received S16020 and 12 received methotrexate . RESULTS A scheduled interim analysis showed one patient having a non-confirmed objective response with S16020 and three patients having a confirmed objective response with methotrexate . In the methotrexate group , there were no patients with severe non-haematological toxicity . With S16020 , there was a high incidence of severe non-haematological toxicities , including asthenia , oedema of the face , oedema and pain at the tumour sites and erythematous rash ; consequently , both studies were stopped . CONCLUSIONS Both studies were stopped due to the poor anticipated benefit/risk ratio for S16020 , although time to progression and overall survival time were similar in both treatment arms We describe a phase III trial on 200 patients with end stage squamous cell carcinoma of the head and neck . The patients were r and omised to one of four treatment arms : cisplatinum alone , methotrexate alone , cisplatinum + 5-FU and cisplatinum + methotrexate . There was no significant difference in the response rates , but the survival of the cisplatinum arm was significantly better than that of the methotrexate arm . The survival of patients receiving cisplatinum as a single agent was longer than that of patients receiving cisplatinum in combination with methotrexate or 5-FU , but not significantly so . Nausea/vomiting and anaemia were significantly more common in the cisplatinum arms than in the methotrexate arm , but the toxicity of combination regimens was not significantly greater than that of cisplatinum used as a single agent PURPOSE To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer , we compared the efficacy and toxicity of cisplatin ( CP ) and fluorouracil ( 5-FU ) , alone and in combination in a phase III trial . PATIENTS AND METHODS Two hundred forty-nine patients with recurrent head and neck cancer were r and omized to one of three treatments :  CP ( 100 mg/m2 ) and 5-FU ( 1 g/m2 x 4 ) , CP , or 5-FU every 3 weeks . RESULTS The overall response rate to the combination ( 32 % ) was superior to that of CP ( 17 % ) or 5-FU ( 13 % ) ( P = .035 ) . Response was associated with good performance status ( PS ) but not with primary site , site of recurrence , histology , prior irradiation , or relative dose intensity . Median time to progression was less than 2.5 months , and there was no significant difference in median survival ( 5.7 months ) among the groups . By multivariate analysis , patients with better PS and poorly differentiated tumors had superior survival . Hematologic toxicity and alopecia were worse in the combination arm . CONCLUSION Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents , survival did not improve Summary Fifty-seven patients with recurrent squamous-cell carcinoma of the head and neck area were r and omized to two different chemotherapeutic regimens . Thirty patients received cis-platinum ( DDP ) alone and 27 patients received a combination of DDP , methotrexate , and bleomycin .  All 57 patients had undergone previous radiation and /or ablative surgery . Of the 30 patients receiving DDP alone , one patient showed a complete response and three a partial response ( 13 % ) . Amongst the 27 patients receiving DDP , methotrexate , and bleomycin , three showed a partial response ( 11 % ) ; there were no complete responders in this group . Major toxicity in the DDP alone group was renal . Renal toxicity and myelosuppression complicated the DDP , methotrexate , and bleomycin group . In summary , the combination of DDP , methotrex 
    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: We report the results of a r and omised phase II trial of docetaxel tested as a single agent in patients with recurrent head and neck cancer using methotrexate as a control arm to vali date the results . Eligibility criteria included : histologically-confirmed squamous cell carcinoma , measurable disease , adequate haematological , renal and hepatic functions , no prior chemotherapy for recurrent cancer , signed informed consent . 40 mg/m2 methotrexate was given as a short weekly bolus i.v . injection , and 40 mg/m2 docetaxel was administered as a one hour weekly infusion . A total of 57 patients were r and omised based on a ratio of 2/1:37 and 20 patients received docetaxel and methotrexate  , respectively . Patient characteristics included 49 males and 8 females ; the median age was 59 years ( range : 43 - 82 years ) . Twenty-eight patients had a local-regional relapse and 29 had distant metastasis , the median disease-free interval was 7.9 months ( range : 0 - 165 months ) . For patients treated with docetaxel , the following grade 3 - 4 toxicities occurred : neutropenia ( 12.5 % ) with febrile neutropenia in one patient ( 1 % ) , anaemia ( 19 % ) mucositis ( 9 % ) and ungueal toxicity ( 9 % ) . In the methotrexate arm , the grade 3 - 4 toxicities were : anaemia ( 15 % ) and mucositis ( 5 % ) . The response rate was significantly higher in the docetaxel arm with 27 % ( 95 % confidence interval ( CI ) : 21.7 - 32.3 % ) of objective responses versus 15 % ( 95 % CI : 11.2 - 18.8 % ) in the methotrexate arm . Overall survival and time to progression were super-imposable between the docetaxel and methotrexate treatments . Docetaxel given as a weekly infusion has a high activity in patients with head and neck cancer . A phase III trial is needed to test if this translates into a survival benefit for docetaxel use A prospect i ve r and omized study was conducted to determine the relative effectiveness , toxicity and tolerance of methotrexate ( MTX ) versus cisplatin ( DDP ) in patients with recurrent head and neck squamous cell carcinoma . Forty‐four patients were r and omized to receive either MTX , 40 mg escalated to 60 mg/m2 IV push weekly , or DDP , 50 mg/m2 6 hour infusion days 1 and 8 every 4 weeks . All patients had objective ly measurable disease and a performance status greater than 60 % ( Karnofsky scale ) . All had been treated with surgery and /or radiotherapy . No patients had prior chemotherapy . Prior treatment , performance status , and site of primary disease were comparable in both groups . Complete and partial objective responses were achieved in 23.5 % of the MTX group and 28.6 % of the DDP group ( P = 0.51 ) . Median duration of response was 84 days in the MTX group and 92 days in the DDP  group . Median survival of patients was 6.1 months with MTX and 6.3 months with DDP  . Mucositis was noted in 38 % of patients in the MTX group ( P = 0.001 ) compared to none in the DDP group . Vomiting occurred in 87 % of patients in the DDP group ( P < .0001 ) compared to 10 % of patients in the MTX group . This study demonstrates that in the treatment of recurrent head and neck squamous cell carcinoma , MTX and DDP are equally effective , although MTX appears to be better tolerated . Cancer 52:206‐210 , 1983 Thirty-eight patients with advanced , inoperable squamous cell carcinoma of the head and neck were r and omized to receive methotrexate alone or methotrexate with Bacillus Calmette-Guérin . The response rates with methotrexate ( 3 of 19 ) and methotrexate plus B. Calmette-Guérin ( 4 of 16 ) were similar , as was the duration of response and survival of the two groups . The results of in vitro immunological studies of lymphocytes were assessed . Marked weight loss , poor performance status , and distant metastases were the most important prognostic factors . The presence of anergy was significantly correlated with weight loss . This study also indicated that a large tumor burden is a frequent occurrence in advanced head and neck cancer and may account for the lack of efficacy of B. Calmette-Guérin One hundred eligible patients with inoperable , locally advanced or metastatic squamous cell carcinoma of the head and neck region following prior therapy were r and omized to receive i m methotrexate ( 50 patients ) or iv cisplatin ( 50 patients ) . Methotrexate produced a complete plus partial response rate of 16.0 % and cisplatin produced a partial response rate of 8.0 % , with median duration s of response of 18 and 8 weeks , respectively . The corresponding median survival times were 20 and 18 weeks . Methotrexate responders survived 60 weeks , versus 17 weeks for nonresponders . The corresponding survival times for cisplatin-treated patients were 38 and 18 weeks . Good pretreatment performance status had a significantly positive effect on survival ( P = 0.04 ) , but prior therapy did not . Toxicity secondary to either agent occurred with the expected frequency . The two agents examined showed comparable antitumor activity in patients with squamous cell carcinoma of the head and neck who had not previously received chemotherapy One hundred ninety‐one patients with recurrent or metastatic squamous cell carcinoma of head and neck origin were allocated at r and om to chemotherapy with conventional‐dose weekly intravenous methotrexate or the combination of cisplatin , vinblastine , and bleomycin . Methotrexate induced responses in 16 of 98 patients ( 16 % ) , whereas 22 of 92 ( 24 % ) responded to the combination regimen ( P = not significant ) . Remission duration ( 20.2 weeks methotrexate ; 15.1 weeks combination ) was similar on both arms , as was survival ( 31.4 weeks methotrexate ; 29.0 weeks combination ) . Therapy was relatively well‐tolerated on both treatment arms , although methotrexate  produced more mucositis and the combination more gastrointestinal and renal toxicity . Response to chemotherapy and disease confined to the locoregional area were associated with somewhat longer survival . Combination chemotherapy as given in this study did not improve any observed parameter , and the results of treatment were poor in both arms A prospect i ve r and omized trial was conducted at Wayne State University , Detroit , Michigan , to compare the efficacy of the combination of high‐dose cis‐diamminodichloroplatinum , Oncovin ( vincristine ) and bleomycin ( COB ) to that of weekly methotrexate ( MTX ) in the induction and maintenance of remission in patients with previously treated advanced squamous cell carcinoma of the head and neck .  Complete response ( CR ) was observed in 11.1 % of patients treated with COB and in 8.3 % of patients treated with weekly methotrexate . The overall response rate ( PR + CR ) was 33.3 % to methotrexate versus 40.7 % to COB . This difference was not significant , nor was the survival of patients treated by either modality . Important variables affecting survival in this study proved to be good performance status ( ⩾70 ) and response to therapy . Nausea and vomiting were the more common side effects of COB ( 56 % ) , while hematologic toxicity was more frequent and more severe in the methotrexate arm ( 75 % ) . Combination chemotherapy with COB is not more effective in producing response or prolonging survival than weekly methotrexate in patients with advanced head and neck carcinoma when both regimens are compared in a r and omized study Summary A phase III 2x2 factorial trial of cisplatinum and bleomycin in 116 patients with recurrent or advanced squamous cell carcinoma of the head and neck is reported . Thirty percent of patients proved to be unfit for chemotherapy , and of those treated progression of tumour was the commonest “ response ” . However , 25 % of patients achieved a partial or complete response , with no significant difference in response rates between the treated arms . The median number of courses received was 1 ( range 0–6 ) and the commonest causes for discontinuation of treatment were renal toxicity and death .  Bleomycin  reduced survival , but not significantly so , whereas cisplatinum  prolonged median survival significantly by 10 weeks . Significant predictors of survival , in addition to treatment by cisplatinum , were age , performance status , N status , number of courses and response of the tumor BACKGROUND The purpose of this study was to carry out two r and omised phase II trials of S16020 , a new olivacine derivative , tested as a single agent in patients with recurrent head and neck cancer , using methotrexate as the control arm to vali date the results . PATIENTS AND METHODS S16020 at either 80 or 100 mg/m2 was administered as a 3-h infusion every 3 weeks . Methotrexate , 40 or 50 mg/m2 , was given by bolus injection , weekly for a minimum of 6 weeks . In total , 36 patients were entered in the r and omised studies ( 25 in an initial study , 11 in a confirmatory study ) of whom 24 received S16020 and 12 received methotrexate . RESULTS A scheduled interim analysis showed one patient having a non-confirmed objective response with S16020 and three patients having a confirmed objective response with methotrexate . In the methotrexate group , there were no patients with severe non-haematological toxicity . With S16020 , there was a high incidence of severe non-haematological toxicities , including asthenia , oedema of the face , oedema and pain at the tumour sites and erythematous rash ; consequently , both studies were stopped . CONCLUSIONS Both studies were stopped due to the poor anticipated benefit/risk ratio for S16020 , although time to progression and overall survival time were similar in both treatment arms We describe a phase III trial on 200 patients with end stage squamous cell carcinoma of the head and neck . The patients were r and omised to one of four treatment arms : cisplatinum alone , methotrexate alone , cisplatinum + 5-FU and cisplatinum + methotrexate . There was no significant difference in the response rates , but the survival of the cisplatinum arm was significantly better than that of the methotrexate arm . The survival of patients receiving cisplatinum as a single agent was longer than that of patients receiving cisplatinum in combination with methotrexate or 5-FU , but not significantly so . Nausea/vomiting and anaemia were significantly more common in the cisplatinum arms than in the methotrexate arm , but the toxicity of combination regimens was not significantly greater than that of cisplatinum used as a single agent PURPOSE To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer , we compared the efficacy and toxicity of cisplatin ( CP ) and fluorouracil ( 5-FU ) , alone and in combination in a phase III trial . PATIENTS AND METHODS Two hundred forty-nine patients with recurrent head and neck cancer were r and omized to one of three treatments :  CP ( 100 mg/m2 ) and 5-FU ( 1 g/m2 x 4 ) , CP , or 5-FU every 3 weeks . RESULTS The overall response rate to the combination ( 32 % ) was superior to that of CP ( 17 % ) or 5-FU ( 13 % ) ( P = .035 ) . Response was associated with good performance status ( PS ) but not with primary site , site of recurrence , histology , prior irradiation , or relative dose intensity . Median time to progression was less than 2.5 months , and there was no significant difference in median survival ( 5.7 months ) among the groups . By multivariate analysis , patients with better PS and poorly differentiated tumors had superior survival . Hematologic toxicity and alopecia were worse in the combination arm . CONCLUSION Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents , survival did not improve Summary Fifty-seven patients with recurrent squamous-cell carcinoma of the head and neck area were r and omized to two different chemotherapeutic regimens . Thirty patients received cis-platinum ( DDP ) alone and 27 patients received a combination of DDP , methotrexate , and bleomycin .  All 57 patients had undergone previous radiation and /or ablative surgery . Of the 30 patients receiving DDP alone , one patient showed a complete response and three a partial response ( 13 % ) . Amongst the 27 patients receiving DDP , methotrexate , and bleomycin , three showed a partial response ( 11 % ) ; there were no complete responders in this group . Major toxicity in the DDP alone group was renal . Renal toxicity and myelosuppression complicated the DDP , methotrexate , and bleomycin group . In summary , the combination of DDP , methotrex 
    Output:
    