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 Topotecan , a camptothecin analog previously approved for the treatment of ovarian cancer and small-cell lung cancer , was granted regular approval by the US Food and Drug Administration ( FDA ) on June 14 , 2006 , for use in combination with cisplatin to treat women with stage IVB , recurrent , or persistent carcinoma of the cervix not amenable to curative treatment with surgery and /or radiation therapy . The purpose of this summary is to review the data base supporting this approval . EXPERIMENTAL DESIGN In a r and omized multicenter study enrolling 293 eligible patients , topotecan plus cisplatin ( TC ) was compared with cisplatin monotherapy . The TC regimen consisted of cisplatin 50 mg/m2 IV over 1 hour on day 1 and topotecan 0.75 mg/m2 IV over 30 minutes on days 1 , 2 , and 3 every 21 days . RESULTS There was a clinical ly relevant and statistically significant improvement in overall survival in the TC treatment arm . Median overall survival was 9.4 months ( 95 % confidence interval [CI]:7.9 - 11.9 ) in the TC arm , compared to 6.5 months ( 95 % CI:5.8 - 8.8 ) with cisplatin alone . The unadjusted hazard ratio for overall survival between treatment arms was 0.76 ( 95 % CI : 0.59 - 0.98 , P = .033 ) favoring the combination arm . The most common toxicities with TC included myelosuppression , nausea and vomiting , mucositis , rash , and hepatotoxicity . CONCLUSIONS This report describes the FDA 's review supporting this first approval of a chemotherapeutic drug for advanced cervical cancer based on demonstration of a survival benefit PURPOSE To prospect ively assess the impact of treatment with cisplatin alone or in combination with topotecan ( CT ) on quality of life ( QOL ) in patients with advanced or recurrent cervical cancer , and to explore the prognostic value of baseline QOL scores . PATIENTS AND METHODS Patients entered on Gynecologic Oncology Group ( GOG ) Protocol 179 were expected to complete QOL assessment s at four time points using Functional Assessment of Cancer Therapy-General ( FACT-G ) , Cervix subscale ( Cx subscale ) , FACT/GOG-Neurotoxicity subscale ( NTX subscale ) , Brief Pain Inventory ( BPI ) , and UNISCALE ( UNI ) . Adjusting for patient age , baseline scores , and effects of time , we longitudinally examined treatment effect on QOL during and after chemotherapy . RESULTS Among patients r and omly allocated to receive cisplatin ( n = 146 ) or CT ( n = 147 ) , there were no statistically significant differences in QOL up to 9 months after r and omization despite more hematologic toxicity in the combination arm . QOL assessment s were completed at rates of 98 % , 85 % , 68 % , and 59 % , respectively , for the four time points , with similar rates and reasons for nonparticipation between regimens . Baseline FACT-G ( P = .0016 ) and BPI ( P = .0001 ) scores were significantly associated with patient age ; older patients had better QOL and less pain . Baseline UNI was positively correlated with FACT-G ( r = 0.66 ; P < .001 ) and Cx subscale ( r = 0.29 ; P < .001 ) , and negatively related to BPI ( r = -0.41 ; P < .0001 ) . Baseline FACT-Cx ( FACT-G + Cx subscale ) was associated with survival . CONCLUSION Despite increased toxicity , CT did not significantly reduce patient QOL when compared with cisplatin alone . Patient-reported QOL measures may be an important prognostic tool in advanced cervix cancer PURPOSE On the basis of reported activity of methotrexate , vinblastine , doxorubicin , and cisplatin ( MVAC ) or topotecan plus cisplatin in advanced cervix cancer , we undertook a r and omized trial comparing these combinations versus cisplatin alone , to determine whether survival is improved with either combination compared with cisplatin alone , and to compare toxicities and quality of life ( QOL ) among the regimens . PATIENTS AND METHODS Eligible patients were r and omly allocated to receive cisplatin 50 mg/m(2 ) every 3 weeks ( CPT ) ; cisplatin 50 mg/m(2 ) day 1 plus topotecan 0.75 mg/m(2 ) days 1 to 3 every 3 weeks ( CT ) ; or methotrexate 30 mg/m(2 ) days 1 , 15 , and 22 , vinblastine 3 mg/m(2 ) days 2 , 15 , and 22 , doxorubicin 30 mg/m(2 ) day 2 , and cisplatin 70 mg/m(2 ) day 2 every 4 weeks ( MVAC ) . Survival was the primary end point ; response rate and progression-free survival ( PFS ) were secondary end points . QOL data are reported separately . RESULTS The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients , and is not included in this analysis . Two hundred ninety-four patients enrolled onto the remaining regimens : 146 to CPT and 147 to CT . Grade 3 to 4 hematologic toxicity was more common with CT . Patients receiving CT had statistically superior outcomes to those receiving CPT , with median overall survival of 9.4 and 6.5 months ( P = .017 ) , median PFS of 4.6 and 2.9 months ( P = .014 ) , and response rates of 27 % and 13 % , respectively . CONCLUSION This is the first r and omized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer Objectives : The Gynecologic Oncology Group performed a r and omized phase II study to determine the antitumor activity and toxicity of two different schedules of administration of bryostatin-1 in patients with persistent or recurrent squamous cell carcinoma of the cervix . Methods : Eligible patients were r and omized to receive either bryostatin-1 25 μg/m2 as a 1-h infusion weekly for 3 weeks followed by a 1-week rest ( Regimen I ) or bryostatin-1 120 μg/m2 as a 72-h continuous infusion every 2 weeks ( Regimen II ) . Results : A total of 70 patients were enrolled on this study . There were 32 eligible patients on Regimen I and 33 eligible patients on Regimen II ; all but 4 had had prior chemotherapy . There were two partial responses ( one on each treatment arm ) among the 65 eligible patients ( response rates = 3.1 and 3.0 % , respectively ) . Ten patients on each regimen had stable disease . The most common adverse event was myalgia ; 8 of 32 patients ( 25 % ) on Regimen I and 16 of 33 patients ( 48 % ) on Regimen II had any grade of myalgia . There was no significant myelosuppression on either treatment arm . Conclusions : Both of these schedules and doses of bryostatin-1 are inactive as single agents in the second-line treatment of squamous cell carcinoma of the cervix PURPOSE Cisplatin , mitolactol ( dibromodulcitol ) , and ifosfamide have been the most active single agents in squamous carcinoma of the cervix identified so far by the Gynecologic Oncology Group ( GOG ) . Combinations of cisplatin plus ifosfamide and cisplatin plus mitolactol are prospect ively compared with cisplatin alone . PATIENTS AND METHODS Patients were r and omized to receive  cisplatin  50 mg/m2 or the same dose of cisplatin plus mitolactol ( C + M ) 180 mg/m2 orally on days 2 to 6 , or cisplatin plus ifosfamide ( CIFX ) 5 g/m2 given as a 24-hour infusion plus mesna 6 g/m2 during and for 12 hours after the ifosfamide infusion , every 3 weeks for up to six courses . Of 454 patients entered , 438 were eligible and analyzed for response and survival . RESULTS CIFX had a higher response rate ( 31.1 % v 17.8 % , p = .004 ) and longer progression-free survival ( PFS ) time ( P = .003 ) compared with cisplatin alone . The median times to progression or death were 4.6 and 3.2 months , respectively . C + M showed no significant improvement in these parameters compared with cisplatin alone . Survival was associated with initial performance score ( PS ; 0 was more favorable ; P < .001 ) and with age ( younger was unfavorable , P = .025 ) . There was no significant difference in overall survival between cisplatin and either of the combinations . Leukopenia , renal toxicity , peripheral neurotoxicity , and CNS toxicity were more frequent with CIFX ( P < .05 ) . CONCLUSION CIFX improved the response rate and PFS duration in advanced cervix cancer compared with cisplatin alone , but at the cost of greater toxicity and with no improvement in survival A total of 394 patients with advanced , measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were r and omized to therapy with either carboplatin or iproplatin . There were 23 patients ineligible for the study and 10 patients who were not evaluable ; the remaining 361 patients were evaluable for response and adverse effects . R and omization was well balanced for age , performance status , and prior therapy . Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin ( 340 mg/m2 if the patient underwent prior radiation ) and 270 mg/m2 for iproplatin ( 230 mg/m2 if the patient underwent prior radiation ) . These doses are equivalent to cisplatin doses of 75 to 100 mg/m2 . Hematologic toxicity was dose-limiting , among which thrombocytopenia was slightly more common than leukopenia . Gastrointestinal toxicity was also prominent with both agents ; however , iproplatin was significantly more toxic than carboplatin ( P less than .001 ) . Renal , otic , and peripheral nervous system toxicities were absent or infrequent with both analogs . No electrolyte abnormalities were observed . The percentage of planned dosages that were actually administered was 100 % of carboplatin doses and 85 % of iproplatin doses ( P less than .0001 ) . The reduction in  iproplatin dose was apparently due to gastrointestinal toxicity . Response rates were similar for both agents ( 15 % for carboplatin , 11 % for iproplatin ) and appear to be inferior to those noted with the parent compound , cisplatin OBJECTIVES The Gynecologic Oncology Group ( GOG ) compared methotrexate , vinblastine , doxorubicin , and cisplatin ( MVAC ) with topotecan and cisplatin ( TC ) or cisplatin alone ( C ) in advanced cervical cancer . The primary endpoint was overall survival ( OS ) , with response rate , progression-free survival ( PFS ) , and quality of life ( QOL ) as secondary objectives . METHODS Eligible patients were r and omly allocated to receive either cisplatin 50 mg/m2 q 3 weeks ( C ) or cisplatin 50 mg/m2 day 1 and topotecan 0.75 mg/m2 days 1 - 3 q 3 weeks ( TC ) or methotrexate 30 mg/m2 days 1 , 15 , and 22 , vinblastine 3 mg/m2 days 2 , 15 , and 22 , doxorubicin 30 mg/m2 day 2 , and cisplatin 70 mg/m2 day 2 q 4 weeks ( MVAC ) . QOL was assessed at four time points using the Functional Assessment of Cancer Therapy-Cervix ( FACT-Cx ) , Neurotoxicity Subscale ( FACT/GOG-NTX subscale ) , and Brief Pain Inventory ( BPI ) .  RESULTS One hundred eighty-six patients ( C = 60 ; TC = 63 ; MVAC = 63 ) were enrolled before MVAC was closed by the GOG Data Safety Monitoring Board after four treatment-related deaths occurred on that arm . MVAC produced a 22 % overall response rate ( 95 % CI : 0.13 to 0.34 ) and median PFS and OS of 4.4 months and 9.4 months , respectively . Compared with C and TC , there was more hematologic toxicity with MVAC . There were no appreciable differences in QOL scores after controlling for baseline scores . CONCLUSIONS MVAC 's clinical activity tended to be similar to that of TC but with an unacceptable risk of death from sepsis at this dose and schedule . Nevertheless , QOL , as measured by these instruments , was not substantially impaired by this regimen This paper reports 
    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 Topotecan , a camptothecin analog previously approved for the treatment of ovarian cancer and small-cell lung cancer , was granted regular approval by the US Food and Drug Administration ( FDA ) on June 14 , 2006 , for use in combination with cisplatin to treat women with stage IVB , recurrent , or persistent carcinoma of the cervix not amenable to curative treatment with surgery and /or radiation therapy . The purpose of this summary is to review the data base supporting this approval . EXPERIMENTAL DESIGN In a r and omized multicenter study enrolling 293 eligible patients , topotecan plus cisplatin ( TC ) was compared with cisplatin monotherapy . The TC regimen consisted of cisplatin 50 mg/m2 IV over 1 hour on day 1 and topotecan 0.75 mg/m2 IV over 30 minutes on days 1 , 2 , and 3 every 21 days . RESULTS There was a clinical ly relevant and statistically significant improvement in overall survival in the TC treatment arm . Median overall survival was 9.4 months ( 95 % confidence interval [CI]:7.9 - 11.9 ) in the TC arm , compared to 6.5 months ( 95 % CI:5.8 - 8.8 ) with cisplatin alone . The unadjusted hazard ratio for overall survival between treatment arms was 0.76 ( 95 % CI : 0.59 - 0.98 , P = .033 ) favoring the combination arm . The most common toxicities with TC included myelosuppression , nausea and vomiting , mucositis , rash , and hepatotoxicity . CONCLUSIONS This report describes the FDA 's review supporting this first approval of a chemotherapeutic drug for advanced cervical cancer based on demonstration of a survival benefit PURPOSE To prospect ively assess the impact of treatment with cisplatin alone or in combination with topotecan ( CT ) on quality of life ( QOL ) in patients with advanced or recurrent cervical cancer , and to explore the prognostic value of baseline QOL scores . PATIENTS AND METHODS Patients entered on Gynecologic Oncology Group ( GOG ) Protocol 179 were expected to complete QOL assessment s at four time points using Functional Assessment of Cancer Therapy-General ( FACT-G ) , Cervix subscale ( Cx subscale ) , FACT/GOG-Neurotoxicity subscale ( NTX subscale ) , Brief Pain Inventory ( BPI ) , and UNISCALE ( UNI ) . Adjusting for patient age , baseline scores , and effects of time , we longitudinally examined treatment effect on QOL during and after chemotherapy . RESULTS Among patients r and omly allocated to receive cisplatin ( n = 146 ) or CT ( n = 147 ) , there were no statistically significant differences in QOL up to 9 months after r and omization despite more hematologic toxicity in the combination arm . QOL assessment s were completed at rates of 98 % , 85 % , 68 % , and 59 % , respectively , for the four time points , with similar rates and reasons for nonparticipation between regimens . Baseline FACT-G ( P = .0016 ) and BPI ( P = .0001 ) scores were significantly associated with patient age ; older patients had better QOL and less pain . Baseline UNI was positively correlated with FACT-G ( r = 0.66 ; P < .001 ) and Cx subscale ( r = 0.29 ; P < .001 ) , and negatively related to BPI ( r = -0.41 ; P < .0001 ) . Baseline FACT-Cx ( FACT-G + Cx subscale ) was associated with survival . CONCLUSION Despite increased toxicity , CT did not significantly reduce patient QOL when compared with cisplatin alone . Patient-reported QOL measures may be an important prognostic tool in advanced cervix cancer PURPOSE On the basis of reported activity of methotrexate , vinblastine , doxorubicin , and cisplatin ( MVAC ) or topotecan plus cisplatin in advanced cervix cancer , we undertook a r and omized trial comparing these combinations versus cisplatin alone , to determine whether survival is improved with either combination compared with cisplatin alone , and to compare toxicities and quality of life ( QOL ) among the regimens . PATIENTS AND METHODS Eligible patients were r and omly allocated to receive cisplatin 50 mg/m(2 ) every 3 weeks ( CPT ) ; cisplatin 50 mg/m(2 ) day 1 plus topotecan 0.75 mg/m(2 ) days 1 to 3 every 3 weeks ( CT ) ; or methotrexate 30 mg/m(2 ) days 1 , 15 , and 22 , vinblastine 3 mg/m(2 ) days 2 , 15 , and 22 , doxorubicin 30 mg/m(2 ) day 2 , and cisplatin 70 mg/m(2 ) day 2 every 4 weeks ( MVAC ) . Survival was the primary end point ; response rate and progression-free survival ( PFS ) were secondary end points . QOL data are reported separately . RESULTS The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients , and is not included in this analysis . Two hundred ninety-four patients enrolled onto the remaining regimens : 146 to CPT and 147 to CT . Grade 3 to 4 hematologic toxicity was more common with CT . Patients receiving CT had statistically superior outcomes to those receiving CPT , with median overall survival of 9.4 and 6.5 months ( P = .017 ) , median PFS of 4.6 and 2.9 months ( P = .014 ) , and response rates of 27 % and 13 % , respectively . CONCLUSION This is the first r and omized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer Objectives : The Gynecologic Oncology Group performed a r and omized phase II study to determine the antitumor activity and toxicity of two different schedules of administration of bryostatin-1 in patients with persistent or recurrent squamous cell carcinoma of the cervix . Methods : Eligible patients were r and omized to receive either bryostatin-1 25 μg/m2 as a 1-h infusion weekly for 3 weeks followed by a 1-week rest ( Regimen I ) or bryostatin-1 120 μg/m2 as a 72-h continuous infusion every 2 weeks ( Regimen II ) . Results : A total of 70 patients were enrolled on this study . There were 32 eligible patients on Regimen I and 33 eligible patients on Regimen II ; all but 4 had had prior chemotherapy . There were two partial responses ( one on each treatment arm ) among the 65 eligible patients ( response rates = 3.1 and 3.0 % , respectively ) . Ten patients on each regimen had stable disease . The most common adverse event was myalgia ; 8 of 32 patients ( 25 % ) on Regimen I and 16 of 33 patients ( 48 % ) on Regimen II had any grade of myalgia . There was no significant myelosuppression on either treatment arm . Conclusions : Both of these schedules and doses of bryostatin-1 are inactive as single agents in the second-line treatment of squamous cell carcinoma of the cervix PURPOSE Cisplatin , mitolactol ( dibromodulcitol ) , and ifosfamide have been the most active single agents in squamous carcinoma of the cervix identified so far by the Gynecologic Oncology Group ( GOG ) . Combinations of cisplatin plus ifosfamide and cisplatin plus mitolactol are prospect ively compared with cisplatin alone . PATIENTS AND METHODS Patients were r and omized to receive  cisplatin  50 mg/m2 or the same dose of cisplatin plus mitolactol ( C + M ) 180 mg/m2 orally on days 2 to 6 , or cisplatin plus ifosfamide ( CIFX ) 5 g/m2 given as a 24-hour infusion plus mesna 6 g/m2 during and for 12 hours after the ifosfamide infusion , every 3 weeks for up to six courses . Of 454 patients entered , 438 were eligible and analyzed for response and survival . RESULTS CIFX had a higher response rate ( 31.1 % v 17.8 % , p = .004 ) and longer progression-free survival ( PFS ) time ( P = .003 ) compared with cisplatin alone . The median times to progression or death were 4.6 and 3.2 months , respectively . C + M showed no significant improvement in these parameters compared with cisplatin alone . Survival was associated with initial performance score ( PS ; 0 was more favorable ; P < .001 ) and with age ( younger was unfavorable , P = .025 ) . There was no significant difference in overall survival between cisplatin and either of the combinations . Leukopenia , renal toxicity , peripheral neurotoxicity , and CNS toxicity were more frequent with CIFX ( P < .05 ) . CONCLUSION CIFX improved the response rate and PFS duration in advanced cervix cancer compared with cisplatin alone , but at the cost of greater toxicity and with no improvement in survival A total of 394 patients with advanced , measurable squamous carcinoma of the uterine cervix and no prior chemotherapy were r and omized to therapy with either carboplatin or iproplatin . There were 23 patients ineligible for the study and 10 patients who were not evaluable ; the remaining 361 patients were evaluable for response and adverse effects . R and omization was well balanced for age , performance status , and prior therapy . Both platinum analogs were given every 28 days with starting doses of 400 mg/m2 for carboplatin ( 340 mg/m2 if the patient underwent prior radiation ) and 270 mg/m2 for iproplatin ( 230 mg/m2 if the patient underwent prior radiation ) . These doses are equivalent to cisplatin doses of 75 to 100 mg/m2 . Hematologic toxicity was dose-limiting , among which thrombocytopenia was slightly more common than leukopenia . Gastrointestinal toxicity was also prominent with both agents ; however , iproplatin was significantly more toxic than carboplatin ( P less than .001 ) . Renal , otic , and peripheral nervous system toxicities were absent or infrequent with both analogs . No electrolyte abnormalities were observed . The percentage of planned dosages that were actually administered was 100 % of carboplatin doses and 85 % of iproplatin doses ( P less than .0001 ) . The reduction in  iproplatin dose was apparently due to gastrointestinal toxicity . Response rates were similar for both agents ( 15 % for carboplatin , 11 % for iproplatin ) and appear to be inferior to those noted with the parent compound , cisplatin OBJECTIVES The Gynecologic Oncology Group ( GOG ) compared methotrexate , vinblastine , doxorubicin , and cisplatin ( MVAC ) with topotecan and cisplatin ( TC ) or cisplatin alone ( C ) in advanced cervical cancer . The primary endpoint was overall survival ( OS ) , with response rate , progression-free survival ( PFS ) , and quality of life ( QOL ) as secondary objectives . METHODS Eligible patients were r and omly allocated to receive either cisplatin 50 mg/m2 q 3 weeks ( C ) or cisplatin 50 mg/m2 day 1 and topotecan 0.75 mg/m2 days 1 - 3 q 3 weeks ( TC ) or methotrexate 30 mg/m2 days 1 , 15 , and 22 , vinblastine 3 mg/m2 days 2 , 15 , and 22 , doxorubicin 30 mg/m2 day 2 , and cisplatin 70 mg/m2 day 2 q 4 weeks ( MVAC ) . QOL was assessed at four time points using the Functional Assessment of Cancer Therapy-Cervix ( FACT-Cx ) , Neurotoxicity Subscale ( FACT/GOG-NTX subscale ) , and Brief Pain Inventory ( BPI ) .  RESULTS One hundred eighty-six patients ( C = 60 ; TC = 63 ; MVAC = 63 ) were enrolled before MVAC was closed by the GOG Data Safety Monitoring Board after four treatment-related deaths occurred on that arm . MVAC produced a 22 % overall response rate ( 95 % CI : 0.13 to 0.34 ) and median PFS and OS of 4.4 months and 9.4 months , respectively . Compared with C and TC , there was more hematologic toxicity with MVAC . There were no appreciable differences in QOL scores after controlling for baseline scores . CONCLUSIONS MVAC 's clinical activity tended to be similar to that of TC but with an unacceptable risk of death from sepsis at this dose and schedule . Nevertheless , QOL , as measured by these instruments , was not substantially impaired by this regimen This paper reports 
    Output:
    