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: The purpose of this study was to establish the maximum tolerated dose ( MTD ) of docetaxel in an outpatient docetaxel ( T ) , cisplatin ( P ) , 5-fluorouracil ( 5-FU ) ( F ) , and leucovorin ( L ) ( opTPFL ) regimen and to obtain preliminary assessment of opTPFL efficacy . Thirty-four patients with stage III or IV squamous cell carcinoma of the head and neck were treated with opTPFL . Docetaxel was escalated from 60 to 95 mg/m2 in combination with 100 mg/m2 cisplatin intravenous bolus , and 2,800 mg/m2 5-FU continuous infusion and 2,000 mg/m2 leucovorin continuous infusion with prophylactic growth factors and antibiotics . Patients who achieved a complete ( CR ) or partial ( PR ) response to three cycles received definitive twice-daily radiation therapy . A total of 97 cycles were administered to 34 patients . The major acute toxicities were neutropenia and mucositis . The MTD of docetaxel was 90 mg/m2 . Seventy-seven of 97 cycles of were administered on an outpatient basis . The overall clinical response rate to opTPFL was 94 % , with 44 % CRs and 50 % PRs . The MTD of opTPFL is 90 mg/m2 docetaxel . Outpatient administration of opTPFL is tolerable , feasible , and does not alter the ability to administer definitive radiation therapy on schedule 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 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 chemotherapy . The primary end point was progression-free survival . RESULTS A total of 358 patients underwent r and omization , with 177 assigned to the TPF group and 181 to the PF group . At a median follow-up of 32.5 months , the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group ( hazard ratio for disease progression or death in the TPF group , 0.72 ; P=0.007 ) . Treatment with TPF result ed in a reduction in the risk of death of 27 % ( P=0.02 ) , with a median overall survival of 18.8 months , as compared with 14.5 months in the PF group . There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia , nausea , vomiting , stomatitis , and hearing loss in the PF group . The rates of death from toxic effects were 2.3 % in the TPF group and 5.5 % in the PF group . CONCLUSIONS As compared with the st and ard regimen of cisplatin and fluorouracil , induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck . ( Clinical Trials.gov number , NCT00003888 [ Clinical Trials.gov ] . ) BACKGROUND We performed a prospect i ve , r and omized study in patients with previously untreated advanced ( Stage III or IV ) laryngeal squamous carcinoma to compare the results of induction chemotherapy followed by definitive radiation therapy with those of conventional laryngectomy and postoperative radiation . METHODS Three hundred thirty-two patients were r and omly assigned to receive either three cycles of chemotherapy ( cisplatin and fluorouracil ) and radiation therapy or surgery and radiation therapy . The clinical tumor response was assessed after two cycles of chemotherapy , and patients with a response received a third cycle followed by definitive radiation therapy ( 6600 to 7600 cGy ) . Patients in whom ther was no tumor response or who had locally recurrent cancers after chemotherapy and radiation therapy underwent salvage laryngectomy .  RESULTS After two cycles of chemotherapy , the clinical tumor response was complete in 31 percent of the patients and partial in 54 percent . After a median follow-up of 33 months , the estimated 2-year survival was 68 percent ( 95 percent confidence interval , 60 to 76 percent ) for both treatment groups ( P = 0.9846 ) . Patterns of recurrence differed significantly between the two groups , with more local recurrences ( P = 0.0005 ) and fewer distant metastases ( P = 0.016 ) in the chemotherapy group than in the surgery group . A total of 59 patients in the chemotherapy group ( 36 percent ) required total laryngectomy . The larynx was preserved in 64 percent of the patients overall and 64 percent of the patients who were alive and free of disease . CONCLUSIONS These preliminary results suggest a new role for chemotherapy in patients with advanced laryngeal cancer and indicate that a treatment strategy involving induction chemotherapy and definitive radiation therapy can be effective in preserving the larynx in a high percentage of patients , without compromising overall survival PURPOSE To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel , cisplatin , and fluorouracil ( FU ; PCF ) versus st and ard cisplatin and FU ( CF ) , both followed by chemoradiotherapy ( CRT ) , in locally advanced head and neck cancer ( HNC ) . PATIENTS AND METHODS Eligibility criteria included biopsy-proven , previously untreated , stage III or IV locally advanced HNC . Patients received either CF ( cisplatin 100 mg/m2 on day 1 plus FU 1000 [ corrected ] mg/m2 continuous infusion on days 1 through 5 ) or PCF ( paclitaxel 175 mg/m2 on day 1 , cisplatin 100 mg/m2 on day 2 , and FU 500 mg/m2 continuous infusion on days 2 through 6 ) ; both regimens were administered for three cycles every 21 days . Patients with complete response ( CR ) or partial response of greater than 80 % in primary tumor received additional CRT ( cisplatin 100 mg/m2 on days 1 , 22 , and 43 plus 70 Gy ) . RESULTS A total of 382 eligible patients were r and omly assigned to CF ( n = 193 ) or PCF ( n = 189 ) . The CR rate was 14 % in the CF arm v 33 % in the PCF arm ( P < .001 ) . Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCF arm ( log-rank test , P = .006 ; Tarone-Ware , P = .003 ) . PCF patients had a trend to longer overall survival ( OS ; 37 months in CF arm v 43 months in PCF arm ; log-rank test , P = .06 ; Tarone-Ware , P = .03 ) . This difference was more evident in patients with unresectable disease ( OS : 26 months in CF arm v 36 months in PCF arm ; log-rank test , P = .04 ; Tarone-Ware , P = .03 ) . CF patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients ( 53 % v 16 % , respectively ; P < .001 ) . CONCLUSION Induction chemotherapy with PCF was better tolerated and result ed in a higher CR rate than CF . However , new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment PURPOSE To determine the safety profile and activity of the combination of docetaxel , cisplatin and 5-fluorouracil ( 5-FU ) in chemotherapy-naive patients with squamous cell carcinoma of the head and neck ( SCCHN ) . PATIENTS AND METHODS Patients with locally advanced unresectable SCCHN were treated with docetaxel and cisplatin both as a 1-h infusion on day 1 followed by a continuous infusion of 5-FU for 5 days . Cycles were planned every 3 weeks up to four cycles , whereafter the patients were treated with locoregional radiotherapy . Two dose levels were studied . Doses in level I were 75 mg/m(2 ) of docetaxel , 75 mg/m(2 ) of cisplatin and 750 mg/m(2)/day of 5-FU ; in level II the cisplatin dose was escalated to 100 mg/m(2 ) . Following chemotherapy , all patients were to receive curative radiotherapy according to the st and ards in the different institutions . RESULTS Twenty-five patients were treated at dose level I with 86 cycles ( median four ; range one to four ) , and 23 at dose level II with 84 cycles ( median four ; range two to four ) . The median relative dose intensity was 0.99 ( range 0.86 - 1.04 ) at level I and 0.94 ( range 0.79 - 1.02 ) at level II . The response rate in the intention-to-treat population was 64 % [ 95 % confidence interval ( CI ) 42.5 % to 82 % ] in level I and 78.3 % ( 95 % CI 56.3 % to 92.5 % ) in level II ; all were partial responses . The maximum tolerated dose was reached at level II with renal toxicity , nausea , stomatitis and thrombocytopenia as principal dose-limiting toxicities . The median survival of the 48 patients was 18.5 months . The survival at 12 , 18 , 24 and 30 months was 69 , 54 , 41 and 31 % , respectively . CONCLUSIONS The combination of docetaxel , cisplatin and 5-FU associated with prophylactic ciprofloxacin is feasible and active in patients with SCCHN . Dose level I is recommended for phase III testing PURPOSE To evaluate the toxicity and efficacy of a 4-day regimen of docetaxel , cisplatin , fluorouracil , and leucovorin ( TPFL4 ) in patients with locoregionally advanced squamous cell carcinoma of the head and neck ( SCCHN ) . PATIENTS AND METHODS Thirty previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status of 2 or less were treated with TPFL4 . Postchemotherapy support included prophylactic growth factors and antibiotics . Patients who achieved a complete response ( CR ) or partial response ( PR ) to three cycles of TPFL4 received definitive twice-daily radiation therapy . The primary end points were toxicity and response to TPFL4 .  RESULTS Eighty-five cycles were administered to 3 
    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: The purpose of this study was to establish the maximum tolerated dose ( MTD ) of docetaxel in an outpatient docetaxel ( T ) , cisplatin ( P ) , 5-fluorouracil ( 5-FU ) ( F ) , and leucovorin ( L ) ( opTPFL ) regimen and to obtain preliminary assessment of opTPFL efficacy . Thirty-four patients with stage III or IV squamous cell carcinoma of the head and neck were treated with opTPFL . Docetaxel was escalated from 60 to 95 mg/m2 in combination with 100 mg/m2 cisplatin intravenous bolus , and 2,800 mg/m2 5-FU continuous infusion and 2,000 mg/m2 leucovorin continuous infusion with prophylactic growth factors and antibiotics . Patients who achieved a complete ( CR ) or partial ( PR ) response to three cycles received definitive twice-daily radiation therapy . A total of 97 cycles were administered to 34 patients . The major acute toxicities were neutropenia and mucositis . The MTD of docetaxel was 90 mg/m2 . Seventy-seven of 97 cycles of were administered on an outpatient basis . The overall clinical response rate to opTPFL was 94 % , with 44 % CRs and 50 % PRs . The MTD of opTPFL is 90 mg/m2 docetaxel . Outpatient administration of opTPFL is tolerable , feasible , and does not alter the ability to administer definitive radiation therapy on schedule 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 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 chemotherapy . The primary end point was progression-free survival . RESULTS A total of 358 patients underwent r and omization , with 177 assigned to the TPF group and 181 to the PF group . At a median follow-up of 32.5 months , the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group ( hazard ratio for disease progression or death in the TPF group , 0.72 ; P=0.007 ) . Treatment with TPF result ed in a reduction in the risk of death of 27 % ( P=0.02 ) , with a median overall survival of 18.8 months , as compared with 14.5 months in the PF group . There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia , nausea , vomiting , stomatitis , and hearing loss in the PF group . The rates of death from toxic effects were 2.3 % in the TPF group and 5.5 % in the PF group . CONCLUSIONS As compared with the st and ard regimen of cisplatin and fluorouracil , induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck . ( Clinical Trials.gov number , NCT00003888 [ Clinical Trials.gov ] . ) BACKGROUND We performed a prospect i ve , r and omized study in patients with previously untreated advanced ( Stage III or IV ) laryngeal squamous carcinoma to compare the results of induction chemotherapy followed by definitive radiation therapy with those of conventional laryngectomy and postoperative radiation . METHODS Three hundred thirty-two patients were r and omly assigned to receive either three cycles of chemotherapy ( cisplatin and fluorouracil ) and radiation therapy or surgery and radiation therapy . The clinical tumor response was assessed after two cycles of chemotherapy , and patients with a response received a third cycle followed by definitive radiation therapy ( 6600 to 7600 cGy ) . Patients in whom ther was no tumor response or who had locally recurrent cancers after chemotherapy and radiation therapy underwent salvage laryngectomy .  RESULTS After two cycles of chemotherapy , the clinical tumor response was complete in 31 percent of the patients and partial in 54 percent . After a median follow-up of 33 months , the estimated 2-year survival was 68 percent ( 95 percent confidence interval , 60 to 76 percent ) for both treatment groups ( P = 0.9846 ) . Patterns of recurrence differed significantly between the two groups , with more local recurrences ( P = 0.0005 ) and fewer distant metastases ( P = 0.016 ) in the chemotherapy group than in the surgery group . A total of 59 patients in the chemotherapy group ( 36 percent ) required total laryngectomy . The larynx was preserved in 64 percent of the patients overall and 64 percent of the patients who were alive and free of disease . CONCLUSIONS These preliminary results suggest a new role for chemotherapy in patients with advanced laryngeal cancer and indicate that a treatment strategy involving induction chemotherapy and definitive radiation therapy can be effective in preserving the larynx in a high percentage of patients , without compromising overall survival PURPOSE To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel , cisplatin , and fluorouracil ( FU ; PCF ) versus st and ard cisplatin and FU ( CF ) , both followed by chemoradiotherapy ( CRT ) , in locally advanced head and neck cancer ( HNC ) . PATIENTS AND METHODS Eligibility criteria included biopsy-proven , previously untreated , stage III or IV locally advanced HNC . Patients received either CF ( cisplatin 100 mg/m2 on day 1 plus FU 1000 [ corrected ] mg/m2 continuous infusion on days 1 through 5 ) or PCF ( paclitaxel 175 mg/m2 on day 1 , cisplatin 100 mg/m2 on day 2 , and FU 500 mg/m2 continuous infusion on days 2 through 6 ) ; both regimens were administered for three cycles every 21 days . Patients with complete response ( CR ) or partial response of greater than 80 % in primary tumor received additional CRT ( cisplatin 100 mg/m2 on days 1 , 22 , and 43 plus 70 Gy ) . RESULTS A total of 382 eligible patients were r and omly assigned to CF ( n = 193 ) or PCF ( n = 189 ) . The CR rate was 14 % in the CF arm v 33 % in the PCF arm ( P < .001 ) . Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCF arm ( log-rank test , P = .006 ; Tarone-Ware , P = .003 ) . PCF patients had a trend to longer overall survival ( OS ; 37 months in CF arm v 43 months in PCF arm ; log-rank test , P = .06 ; Tarone-Ware , P = .03 ) . This difference was more evident in patients with unresectable disease ( OS : 26 months in CF arm v 36 months in PCF arm ; log-rank test , P = .04 ; Tarone-Ware , P = .03 ) . CF patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients ( 53 % v 16 % , respectively ; P < .001 ) . CONCLUSION Induction chemotherapy with PCF was better tolerated and result ed in a higher CR rate than CF . However , new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment PURPOSE To determine the safety profile and activity of the combination of docetaxel , cisplatin and 5-fluorouracil ( 5-FU ) in chemotherapy-naive patients with squamous cell carcinoma of the head and neck ( SCCHN ) . PATIENTS AND METHODS Patients with locally advanced unresectable SCCHN were treated with docetaxel and cisplatin both as a 1-h infusion on day 1 followed by a continuous infusion of 5-FU for 5 days . Cycles were planned every 3 weeks up to four cycles , whereafter the patients were treated with locoregional radiotherapy . Two dose levels were studied . Doses in level I were 75 mg/m(2 ) of docetaxel , 75 mg/m(2 ) of cisplatin and 750 mg/m(2)/day of 5-FU ; in level II the cisplatin dose was escalated to 100 mg/m(2 ) . Following chemotherapy , all patients were to receive curative radiotherapy according to the st and ards in the different institutions . RESULTS Twenty-five patients were treated at dose level I with 86 cycles ( median four ; range one to four ) , and 23 at dose level II with 84 cycles ( median four ; range two to four ) . The median relative dose intensity was 0.99 ( range 0.86 - 1.04 ) at level I and 0.94 ( range 0.79 - 1.02 ) at level II . The response rate in the intention-to-treat population was 64 % [ 95 % confidence interval ( CI ) 42.5 % to 82 % ] in level I and 78.3 % ( 95 % CI 56.3 % to 92.5 % ) in level II ; all were partial responses . The maximum tolerated dose was reached at level II with renal toxicity , nausea , stomatitis and thrombocytopenia as principal dose-limiting toxicities . The median survival of the 48 patients was 18.5 months . The survival at 12 , 18 , 24 and 30 months was 69 , 54 , 41 and 31 % , respectively . CONCLUSIONS The combination of docetaxel , cisplatin and 5-FU associated with prophylactic ciprofloxacin is feasible and active in patients with SCCHN . Dose level I is recommended for phase III testing PURPOSE To evaluate the toxicity and efficacy of a 4-day regimen of docetaxel , cisplatin , fluorouracil , and leucovorin ( TPFL4 ) in patients with locoregionally advanced squamous cell carcinoma of the head and neck ( SCCHN ) . PATIENTS AND METHODS Thirty previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status of 2 or less were treated with TPFL4 . Postchemotherapy support included prophylactic growth factors and antibiotics . Patients who achieved a complete response ( CR ) or partial response ( PR ) to three cycles of TPFL4 received definitive twice-daily radiation therapy . The primary end points were toxicity and response to TPFL4 .  RESULTS Eighty-five cycles were administered to 3 
    Output:
    