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 The objectives of this prospect i ve r and omized study of consolidation therapy were to evaluate recurrence-free survival ( RFS ) , overall survival ( OS ) , and the morbidity of intraperitoneal ( IP ) chromic phosphate suspension ( 32P ) therapy in patients with stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy ( SLL ) procedure after primary chemotherapy . PATIENTS AND METHODS In a multi-institution clinical cooperative trial , 202 eligible patients with a negative SLL were r and omly selected to receive either 15 mCi IP 32P ( n = 104 ) or no further therapy ( NFT ; n = 98 ) . RESULTS With a median follow-up of 63 months in living patients , 68 patients in the IP 32P group ( 65 % ) and 63 patients in the NFT group ( 64 % ) have developed tumor recurrence . The relative risk of recurrence is 0.90 ( IP 32P to NFT ) ( 90 % confidence interval [ CI ] , 0.68 to 1.19 ) . The 5-year RFS rate is 42 % and 36 % for the IP 32P and NFT groups , respectively ; the difference is not statistically significant ( log-rank test , P = .27 ) . There was no statistically significant difference in OS ( P = .19 ) . The relative risk of death is 0.85 ( IP 32P to NFT ) ( 90 % CI , 0.62 to 1.16 ) . Sixteen patients ( 8 % ) experienced grade 3 or 4 adverse effects , with eight in each respective group . CONCLUSION Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative SLL . Despite complete pathologic remission at SLL after initial surgery and platinum-based chemotherapy , 61 % of stage III ovarian cancer patients had tumor recurrence within 5 years of negative SLL . This indicates a need for more effective initial therapy and further studies of consolidation therapy 5006 Background : Phase II studies have suggested that HDC is most effective in chemosensitive AOC pts with low tumor burden . METHODS We compared the disease free-survival ( DFS ) , overall survival ( OS ) and toxicity of women with AOC r and omized after second-look surgery ( SLS ) to receive either HDC Carboplatin-Cyclophosphamide and PBSC support ( Cb 400 mg/m2/d and Cy 1500 mg/m2/d x 4 days ) or 3 cycles of conventional-dose maintenance ( CDM ) ( q4w , Cb 300 mg/m2 , Cy 500 mg/m2 ) . Eligibility criteria were : age < 60 yrs , FIGO stage III-IV , disease responsive to 4 - 6 cycles of a platinum-based first-line chemotherapy , tumor size < 2 cm at the end of the SLS or a pathological complete response ( pCR ) but high-risk factors . RESULTS Between 07/1995 to 10/2000 , 110 pts were enrolled , 57 in the HDC and 53 in the CDM arm . Pts characteristics were well balanced between the 2 arms . Half of the pts received paclitaxel in first-line . Nine pts had Stage IV and 101 pts stage III with at SLS : pCR ( 39 % ) , microscopic ( 20 % ) and macroscopic ( 41 % ) disease . In the HDC arm , 1 pt was ineligible and 11 ( 20 % ) did not receive the HDC because of poor PBSC mobilization ( n= 7 ) , pt refusal ( n=3 ) or early relapse ( n=1 ) . Median time to neutrophil and platelet recovery was 11 days . Two pts died from toxic myocarditis and renal insufficiency respectively . Median follow-up is 60 months . At time of analysis , 94 pts have relapsed and 63 have died . DFS and OS were not significantly different between the 2 arms . Median DFS and OS from r and omization were 12.2 ( 95 % CI : 7.3 - 17.1 ) and 42.5 ( 95 % CI : 28.8 - 56.6 ) months in the CDM arm , and were 17.5 ( 95 % CI : 5.2 - 29.9 ) ( p=.22 ) and 49.7 ( 95 % CI : 29.9 - 69.4 ) ( p=.43 ) months in the HDC arm , respectively . CONCLUSIONS These data do not support high-dose consolidation chemotherapy in AOC . [ Table : see text ] Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently PURPOSE Pazopanib is an oral , multikinase inhibitor of vascular endothelial growth factor receptor ( VEGFR ) -1/-2/-3 , platelet-derived growth factor receptor ( PDGFR ) -α/-β , and c-Kit . Pre clinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment . This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy . PATIENTS AND METHODS Nine hundred forty patients with histologically confirmed cancer of the ovary , fallopian tube , or peritoneum , International Federation Gynecology Obstetrics ( FIGO ) stages II-IV , no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy  were r and omized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months . The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators . RESULTS Maintenance pazopanib  prolonged progression-free survival  compared with placebo ( hazard ratio [ HR ] , 0.77 ; 95 % CI , 0.64 to 0.91 ; P = .0021 ; median , 17.9 v 12.3 months , respectively ) . Interim survival analysis based on events in 35.6 % of the population did not show any significant difference . Grade 3 or 4 adverse events of hypertension ( 30.8 % ) , neutropenia ( 9.9 % ) , liver-related toxicity ( 9.4 % ) , diarrhea ( 8.2 % ) , fatigue ( 2.7 % ) , thrombocytopenia ( 2.5 % ) , and palmar-plantar erythrodysesthesia ( 1.9 % ) were significantly higher in the pazopanib arm . Treatment discontinuation related to adverse events was higher among patients treated with pazopanib ( 33.3 % ) compared with placebo ( 5.6 % ) . CONCLUSION Pazopanib maintenance therapy provided a median improvement of 5.6 months ( HR , 0.77 ) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy . Overall survival data to this point did not suggest any benefit . Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity ( NCT00866697 ) The aim of this study is to evaluate the efficacy of three additional cycles of paclitaxel and platinum chemotherapy in epithelial ovarian cancer patients with clinical complete response ( CR ) . Patients with histologically confirmed epithelial ovarian cancer stages II – IV with clinical CR after primary surgery and six cycles of chemotherapy with paclitaxel/platinum entered into the study . Three cycles of paclitaxel/platinum ( cisplatin , carboplatin ) were administered as a consolidation chemotherapy only in patients who agreed to the informed consent . Patients without further treatment served as controls . A total of 81 patients entered into the study . According to the informed consent , 42 patients were treated by the consolidation chemotherapy , and 39 patients were followed up without further treatment .  The median actuarial disease-free survival for the patients with and without consolidation chemotherapy was 25.0 months and 26.0 months , respectively ( P = 0.80 ) . The median overall survival is not reached . World Health Organization grade 3–4 toxicities in the consolidation arm were increased but showed no significant differences statistically . Although the sample size is small and not r and omized , these results suggest that three cycles of consolidation chemotherapy with paclitaxel/platinum might not provide a favorable outcome in patients with a clinical CR PURPOSE To determine whether continuing paclitaxel for an extended time period in women with advanced ovarian cancer who had achieved a clinical ly defined complete response to a platinum/paclitaxel-based chemotherapy  could prolong subsequent progression-free survival ( PFS ) and affect ultimate survival . PATIENTS AND METHODS Patients were r and omly assigned to either three or 12 cycles of single-agent paclitaxel administered every 28 days and were then followed up for progression-free and overall survival . RESULTS As of September 6 , 2001 , 277 patients ( 262 assessable ) had entered the trial , with a total of 54 PFS events having developed among 222 patients with follow-up data . With the exception of peripheral neuropathy , there were no major differences in toxicity between the regimens . The median PFS was 21 and 28 months in the three-cycle and 12-cycle paclitaxel arms , respectively . One-sided P values from an unadjusted log-rank test and an adjusted Cox model analysis ( for stratification factors ) were.0035 and .0023 , respectively , both in favor of the 12-cycle arm . The Cox model-adjusted three-cycle versus the 12-cycle progression hazard ratio was estimated to be 2.31 ( 99 % confidence interval , 1.08 to 4.94 ) . With a protocol -specified early termination boundary of P = .005 , these findings led the Southwest Oncology Group Data Safety Monitoring Committee to discontinue the trial . As of the date of study closure , there was no difference in overall survival between the treatment arms . CONCLUSION Twelve cycles of single-agent paclitaxel administered to women with advanced ovarian cancer who attain a clinical ly defined complete response to initial platinum/paclitaxel-based chemotherapy significantly prolongs the duration of PFS Five versus ten cycles of cyclophosphamide , doxorubicin , and cisplatin ( CAP ) were compared in advanced ovarian carcinoma by a prospect i ve r and omized study of 78 patients , 41 receiving 5 cycles ( CAP5 ) and 37 receiving 10 cycles ( CAP10 ) of chemotherapy .  Patients were stratified by histologic grade and size of residual disease . Cyclophosphamide , 600 mg/m2 , doxorubicin , 40 mg/m2 , and cisplatin , 100 mg/m2 , were administered every 4 weeks for 5 or 10 cycles . Second-look laparotomy was performed to evaluate response and plan further therapy . CAP5 patients found a second-look laparotomy to have partially responded to chemotherapy were treated with 5 additional cycles of CAP . CAP10 was more toxic than CAP5 with respect to myelosuppression , hospital admissions for nadir fever , median elevation of creatinine , and degree of peripheral neuropathy . Median follow-up is 64 months . CAP5 and CAP10 were equivalent in surgically documented complete responses ( 34 versus 35 % ) and survival ( P = 0.41 ) . Twelve partial responders to CAP5 received additional CAP chemotherapy ; one complete response result ed . We conclude that CAP5 is preferable to CAP10 in treatment of advanced ovarian cancer as it is equally effective and less toxic INTRODUCTION R and omized trials have demonstrated significant improvements in progression-free survival ( PFS ) with consolidation paclitaxel ( P ) and bevacizumab ( B )  following cytoreduction and adjuvant carboplatin/paclitaxel ( CP ) for advanced epithelial ovarian cancer ( EOC ) . We sought to evaluate the cost-effectiveness ( C/E ) of these consolidation strategies . METHODS A decision model was developed based on Gynecologic Oncology Group ( GOG ) 
    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 The objectives of this prospect i ve r and omized study of consolidation therapy were to evaluate recurrence-free survival ( RFS ) , overall survival ( OS ) , and the morbidity of intraperitoneal ( IP ) chromic phosphate suspension ( 32P ) therapy in patients with stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy ( SLL ) procedure after primary chemotherapy . PATIENTS AND METHODS In a multi-institution clinical cooperative trial , 202 eligible patients with a negative SLL were r and omly selected to receive either 15 mCi IP 32P ( n = 104 ) or no further therapy ( NFT ; n = 98 ) . RESULTS With a median follow-up of 63 months in living patients , 68 patients in the IP 32P group ( 65 % ) and 63 patients in the NFT group ( 64 % ) have developed tumor recurrence . The relative risk of recurrence is 0.90 ( IP 32P to NFT ) ( 90 % confidence interval [ CI ] , 0.68 to 1.19 ) . The 5-year RFS rate is 42 % and 36 % for the IP 32P and NFT groups , respectively ; the difference is not statistically significant ( log-rank test , P = .27 ) . There was no statistically significant difference in OS ( P = .19 ) . The relative risk of death is 0.85 ( IP 32P to NFT ) ( 90 % CI , 0.62 to 1.16 ) . Sixteen patients ( 8 % ) experienced grade 3 or 4 adverse effects , with eight in each respective group . CONCLUSION Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative SLL . Despite complete pathologic remission at SLL after initial surgery and platinum-based chemotherapy , 61 % of stage III ovarian cancer patients had tumor recurrence within 5 years of negative SLL . This indicates a need for more effective initial therapy and further studies of consolidation therapy 5006 Background : Phase II studies have suggested that HDC is most effective in chemosensitive AOC pts with low tumor burden . METHODS We compared the disease free-survival ( DFS ) , overall survival ( OS ) and toxicity of women with AOC r and omized after second-look surgery ( SLS ) to receive either HDC Carboplatin-Cyclophosphamide and PBSC support ( Cb 400 mg/m2/d and Cy 1500 mg/m2/d x 4 days ) or 3 cycles of conventional-dose maintenance ( CDM ) ( q4w , Cb 300 mg/m2 , Cy 500 mg/m2 ) . Eligibility criteria were : age < 60 yrs , FIGO stage III-IV , disease responsive to 4 - 6 cycles of a platinum-based first-line chemotherapy , tumor size < 2 cm at the end of the SLS or a pathological complete response ( pCR ) but high-risk factors . RESULTS Between 07/1995 to 10/2000 , 110 pts were enrolled , 57 in the HDC and 53 in the CDM arm . Pts characteristics were well balanced between the 2 arms . Half of the pts received paclitaxel in first-line . Nine pts had Stage IV and 101 pts stage III with at SLS : pCR ( 39 % ) , microscopic ( 20 % ) and macroscopic ( 41 % ) disease . In the HDC arm , 1 pt was ineligible and 11 ( 20 % ) did not receive the HDC because of poor PBSC mobilization ( n= 7 ) , pt refusal ( n=3 ) or early relapse ( n=1 ) . Median time to neutrophil and platelet recovery was 11 days . Two pts died from toxic myocarditis and renal insufficiency respectively . Median follow-up is 60 months . At time of analysis , 94 pts have relapsed and 63 have died . DFS and OS were not significantly different between the 2 arms . Median DFS and OS from r and omization were 12.2 ( 95 % CI : 7.3 - 17.1 ) and 42.5 ( 95 % CI : 28.8 - 56.6 ) months in the CDM arm , and were 17.5 ( 95 % CI : 5.2 - 29.9 ) ( p=.22 ) and 49.7 ( 95 % CI : 29.9 - 69.4 ) ( p=.43 ) months in the HDC arm , respectively . CONCLUSIONS These data do not support high-dose consolidation chemotherapy in AOC . [ Table : see text ] Background The grading of recommendation , assessment , development and evaluation ( GRADE ) approach is widely implemented in health technology assessment and guideline development organisations throughout the world . GRADE provides a transparent approach to reaching judgements about the quality of evidence on the effects of a health care intervention , but is complex and therefore challenging to apply in a consistent manner . Methods We developed a checklist to guide the research er to extract the data required to make a GRADE assessment . We applied the checklist to 29 meta-analyses of r and omised controlled trials on the effectiveness of health care interventions . Two review ers used the checklist for each paper and used these data to rate the quality of evidence for a particular outcome . Results For most ( 70 % ) checklist items , there was good agreement between review ers . The main problems were for items relating to indirectness where considerable judgement is required . Conclusions There was consistent agreement between review ers on most items in the checklist . The use of this checklist may be an aid to improving the consistency and reproducibility of GRADE assessment s , particularly for inexperienced users or in rapid review s without the re sources to conduct assessment s by two research ers independently PURPOSE Pazopanib is an oral , multikinase inhibitor of vascular endothelial growth factor receptor ( VEGFR ) -1/-2/-3 , platelet-derived growth factor receptor ( PDGFR ) -α/-β , and c-Kit . Pre clinical and clinical studies support VEGFR and PDGFR as targets for advanced ovarian cancer treatment . This study evaluated the role of pazopanib maintenance therapy in patients with ovarian cancer whose disease did not progress during first-line chemotherapy . PATIENTS AND METHODS Nine hundred forty patients with histologically confirmed cancer of the ovary , fallopian tube , or peritoneum , International Federation Gynecology Obstetrics ( FIGO ) stages II-IV , no evidence of progression after primary therapy consisting of surgery and at least five cycles of platinum-taxane chemotherapy  were r and omized 1:1 to receive pazopanib 800 mg once per day or placebo for up to 24 months . The primary end point was progression-free survival by RECIST 1.0 assessed by the investigators . RESULTS Maintenance pazopanib  prolonged progression-free survival  compared with placebo ( hazard ratio [ HR ] , 0.77 ; 95 % CI , 0.64 to 0.91 ; P = .0021 ; median , 17.9 v 12.3 months , respectively ) . Interim survival analysis based on events in 35.6 % of the population did not show any significant difference . Grade 3 or 4 adverse events of hypertension ( 30.8 % ) , neutropenia ( 9.9 % ) , liver-related toxicity ( 9.4 % ) , diarrhea ( 8.2 % ) , fatigue ( 2.7 % ) , thrombocytopenia ( 2.5 % ) , and palmar-plantar erythrodysesthesia ( 1.9 % ) were significantly higher in the pazopanib arm . Treatment discontinuation related to adverse events was higher among patients treated with pazopanib ( 33.3 % ) compared with placebo ( 5.6 % ) . CONCLUSION Pazopanib maintenance therapy provided a median improvement of 5.6 months ( HR , 0.77 ) in progression-free survival in patients with advanced ovarian cancer who have not progressed after first-line chemotherapy . Overall survival data to this point did not suggest any benefit . Additional analysis should help to identify subgroups of patients in whom improved efficacy may balance toxicity ( NCT00866697 ) The aim of this study is to evaluate the efficacy of three additional cycles of paclitaxel and platinum chemotherapy in epithelial ovarian cancer patients with clinical complete response ( CR ) . Patients with histologically confirmed epithelial ovarian cancer stages II – IV with clinical CR after primary surgery and six cycles of chemotherapy with paclitaxel/platinum entered into the study . Three cycles of paclitaxel/platinum ( cisplatin , carboplatin ) were administered as a consolidation chemotherapy only in patients who agreed to the informed consent . Patients without further treatment served as controls . A total of 81 patients entered into the study . According to the informed consent , 42 patients were treated by the consolidation chemotherapy , and 39 patients were followed up without further treatment .  The median actuarial disease-free survival for the patients with and without consolidation chemotherapy was 25.0 months and 26.0 months , respectively ( P = 0.80 ) . The median overall survival is not reached . World Health Organization grade 3–4 toxicities in the consolidation arm were increased but showed no significant differences statistically . Although the sample size is small and not r and omized , these results suggest that three cycles of consolidation chemotherapy with paclitaxel/platinum might not provide a favorable outcome in patients with a clinical CR PURPOSE To determine whether continuing paclitaxel for an extended time period in women with advanced ovarian cancer who had achieved a clinical ly defined complete response to a platinum/paclitaxel-based chemotherapy  could prolong subsequent progression-free survival ( PFS ) and affect ultimate survival . PATIENTS AND METHODS Patients were r and omly assigned to either three or 12 cycles of single-agent paclitaxel administered every 28 days and were then followed up for progression-free and overall survival . RESULTS As of September 6 , 2001 , 277 patients ( 262 assessable ) had entered the trial , with a total of 54 PFS events having developed among 222 patients with follow-up data . With the exception of peripheral neuropathy , there were no major differences in toxicity between the regimens . The median PFS was 21 and 28 months in the three-cycle and 12-cycle paclitaxel arms , respectively . One-sided P values from an unadjusted log-rank test and an adjusted Cox model analysis ( for stratification factors ) were.0035 and .0023 , respectively , both in favor of the 12-cycle arm . The Cox model-adjusted three-cycle versus the 12-cycle progression hazard ratio was estimated to be 2.31 ( 99 % confidence interval , 1.08 to 4.94 ) . With a protocol -specified early termination boundary of P = .005 , these findings led the Southwest Oncology Group Data Safety Monitoring Committee to discontinue the trial . As of the date of study closure , there was no difference in overall survival between the treatment arms . CONCLUSION Twelve cycles of single-agent paclitaxel administered to women with advanced ovarian cancer who attain a clinical ly defined complete response to initial platinum/paclitaxel-based chemotherapy significantly prolongs the duration of PFS Five versus ten cycles of cyclophosphamide , doxorubicin , and cisplatin ( CAP ) were compared in advanced ovarian carcinoma by a prospect i ve r and omized study of 78 patients , 41 receiving 5 cycles ( CAP5 ) and 37 receiving 10 cycles ( CAP10 ) of chemotherapy .  Patients were stratified by histologic grade and size of residual disease . Cyclophosphamide , 600 mg/m2 , doxorubicin , 40 mg/m2 , and cisplatin , 100 mg/m2 , were administered every 4 weeks for 5 or 10 cycles . Second-look laparotomy was performed to evaluate response and plan further therapy . CAP5 patients found a second-look laparotomy to have partially responded to chemotherapy were treated with 5 additional cycles of CAP . CAP10 was more toxic than CAP5 with respect to myelosuppression , hospital admissions for nadir fever , median elevation of creatinine , and degree of peripheral neuropathy . Median follow-up is 64 months . CAP5 and CAP10 were equivalent in surgically documented complete responses ( 34 versus 35 % ) and survival ( P = 0.41 ) . Twelve partial responders to CAP5 received additional CAP chemotherapy ; one complete response result ed . We conclude that CAP5 is preferable to CAP10 in treatment of advanced ovarian cancer as it is equally effective and less toxic INTRODUCTION R and omized trials have demonstrated significant improvements in progression-free survival ( PFS ) with consolidation paclitaxel ( P ) and bevacizumab ( B )  following cytoreduction and adjuvant carboplatin/paclitaxel ( CP ) for advanced epithelial ovarian cancer ( EOC ) . We sought to evaluate the cost-effectiveness ( C/E ) of these consolidation strategies . METHODS A decision model was developed based on Gynecologic Oncology Group ( GOG ) 
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