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: OBJECTIVE Serum CA-125 values have been advocated in the monitoring of ovarian cancer patients receiving intravenous ( IV ) chemotherapy .  This evaluation sought to determine if the CA-125 test can be used to monitor treatment effect among patients receiving intraperitoneal chemotherapy ( IP ) .  METHODS Patient charts from a phase III clinical trial ( GOG 172 ) were retrospectively review ed . Serum CA-125 levels prior to each cycle of therapy were collected and compared between the IV and IP chemotherapy delivery . The association between CA-125 and progression-free survival ( PFS ) or overall survival ( OS ) was estimated and the homogeneity of the results between IP and IV chemotherapy was assessed . RESULTS A total of 177 patients were treated with IV chemotherapy and 165 patients with IP chemotherapy with CA-125 data available were included in this analysis . The observed difference was not statistically significant in median CA-125 levels between the IV and IP arms at any time point ( P>0.05 for all ) . Following surgery and adjuvant chemotherapy , patients with an abnormal CA-125 > 35 U/ml were 2.45 times more likely to have disease progression ( 95 % CI : 1.52 - 3.95 , P<0.001 ) and 2.78 times more likely to die of disease ( 95 % CI : 1.66 - 4.65 , P<0.001 ) , compared to those with a CA-125 < 35 U/ml . These results were consistent with IP and IV chemotherapy . CONCLUSION Serum CA-125 levels decrease in a similar manner during IP chemotherapy when compared to IV chemotherapy . Serum CA-125 algorithms for monitoring treatment effect that have been established for IV chemotherapy may also be applied for patients receiving IP chemotherapy OBJECTIVE To compare the survival between intraperitoneal cisplatin-based chemotherapy ( IPCT ) and intravenous cisplatin-based chemotherapy ( IVCT ) in stage III epithelial ovarian cancer with minimal residual disease ( < 1 cm ) after primary debulking surgery . METHOD One hundred and thirty-two patients with stage III epithelial ovarian cancer after optimal primary debulking surgery with minimal residual disease between April 1990 and March 1995 were entered into a r and omized clinical trial in which IPCT or IVCT was administered at 3-week intervals . Patients in the IPCT arm received cisplatin-based ( 100 mg/m(2 ) ) intraperitoneal chemotherapy . Patients in the IVCT arm received cisplatin-based ( 50 mg/m(2 ) ) intravenous chemotherapy . The tumor response was assessed every 3 months . The hematological toxicity using the South West Oncology Group ( SWOG ) toxicity criteria was assessed . Catheter complications associated with intraperitoneal chemotherapy were also analyzed . RESULT The estimated median survival in the IPCT group was 43 months ( 95 % confidence interval , 34 - 54 ) and IVCT group was 48 months ( 95 % confidence interval , 37 - 59 ) . The hazard ratio of death was not statistically significant between IPCT and IVCT ( hazard ratio , 1.13 ; 95 % CI , 0.69 - 1.86 ; P=0.317 ) . The frequencies of hematological toxic effects were significantly lower in the IPCT group than in the IVCT group . CONCLUSION Intravenous and intraperitoneal chemotherapy are associated with equivalent survival in patients with minimal residual stage III epithelial ovarian cancer after optimal cytoreductive surgery Purpose : To assess the antitumor efficacy and safety of 2 treatment modalities : intraperitoneal carboplatin combined with intravenous ( IV ) paclitaxel . Patients and Methods : Eligible patients were those with epithelial ovarian carcinoma or primary peritoneal carcinoma stages II to IV who underwent initial surgery and had a residual tumor size of 2 cm or larger . Patients received IV paclitaxel 175 mg/m2 followed by intraperitoneal carboplatin AUC6 . The primary end point was a response . Secondary end points were toxicity , progression-free survival , and overall survival . Results : Twenty-six patients were enrolled , and 24 patients were eligible for assessment . The response rate was 83.3 % ( 95 % CI , 62.6%-95.3 % ; Table 4 ) . The median progression-free survival was 25 months . The median overall survival had not been reached . Incidences of grade ( G ) 3/4 hematological toxicities were absolute neutrophil count , 96 % ; hemoglobin , 29 % ; and thrombocytopenia , 16 % . Nonhematological toxicities included G2 liver function , 4 % ; G3 sensory neuropathy , 8 % ; and G3 myalgia and arthralgia , 4 % . Conclusions : Intraperitoneal administration of carboplatin combined with IV paclitaxel was well tolerated and showed satisfactory response in the patients with bulky residual tumor . Large-scale phase III trial comparing with IV carboplatin is warranted in this patient population Summary The currently accepted therapies for ovarian cancer have produced only limited numbers of extended complete remissions in advanced-stage disease . Studies of high-volume intraperitoneal chemotherapy have been initiated to define the toxicology , pharmacokinetics , and the therapeutic effectiveness of this treatment modality . This technique has been virtually ignored until recently , because little success has been achieved with it except in one study ( Rutledge , 1966 ) , in which large intraperitoneal fluid volumes were used . The general lack of success probably reflects inadequate attention to physiologic and pharmacologic principles of drug distribution and absorption in a space as large as the peritoneal cavity . Biomedical engineers , pharmacologists , and clinicians at the NCI have cooperated in the development of a rational chemotherapy for ovarian cancer . Following mathematical pharmacokinetic modeling and toxicologic studies in rat , a Phase I clinical trial of intraperitoneal methotrexate administered in large volumes of dialysis fluid was initiated . Results in three patients confirm the practicality of this approach , and further investigation is warranted A phase III study was conducted comparing intraperitoneal ( ip ) versus intravenous ( iv ) cisplatin-based therapy for patients with newly diagnosed ovarian cancer to determine if the pharmacologic advantage of ip delivery could be translated into an improved response and survival rate .  Twenty-nine patients were r and omized to receive six cycles of ip cisplatin 200 mg/m2 plus ip etoposide 350 mg/m2 with iv thiosulfate protection given every 4 weeks ; thirty-three patients were r and omized to receive six cycles of iv cisplatin 100 mg/m2 plus iv cyclophosphamide 600 mg/m2 administered every 3 weeks . Patients were stratified by stage ( IIC-IV ) and size of residual disease ( > or < or = 1 cm ) . The study was conducted in a community-wide setting . The complete response in evaluable patients was 48 % in the ip group and 52 % in the iv group . The surgical complete response rate for all patients on study , underestimated because not all patients in complete clinical remission had a second-look laparotomy , was 31 % in the ip group and 33 % in the iv group . There was no difference in the response rates between the treatment arms as a function of residual disease < or = or > 1 cm . With a median follow-up of 46 months ( range 21 - 70 months ) there is no difference in response duration or survival . Both regimens were well tolerated with comparable hematologic and nonhematologic toxicity Retrospective studies and a Phase II trial demonstrated the promising efficacy and safety of intraperitoneal administration of carboplatin in ovarian , fallopian tube and primary peritoneal cancer . A Japanese Gynecologic Oncology Group 3016 r and omized Phase III trial for these cancers showed dose-dense weekly administration of paclitaxel significant improvement of progression-free survival and overall survival over every 3-week administration . From June 2010 , we have been conducting a r and omized Phase II/III trial of intravenous versus intraperitoneal administration of carboplatin every 3 week in combination with dose-dense weekly administration of paclitaxel . The purpose of this trial is to prove the superiority of intraperitoneal administration of carboplatin over intravenous administration . Primary endpoint is progression-free survival and secondary endpoints include overall survival , quality of life assessment and cost-benefit .  The first 120 patients will be evaluated for the feasibility of intraperitoneal arm and a total of 746 patients will be enrolled in a Phase III study OBJECTIVE Intraperitoneal ( IP ) chemotherapy has gained enthusiasm in the treatment of ovarian cancer . Despite having a better survival advantage than intravenous ( IV ) chemotherapy , IP chemotherapy still poses significant morbidity and complications . Identifying the subset of patients who could best benefit from IP chemotherapy  , and those who would least benefit from this treatment , thus avoiding potential complications , is critical . METHODS Between January 2001 and December 2007 , 367 patients with stage III epithelial ovarian cancer underwent r and omized trial for IP/IV chemotherapy  were recruited to construct a nomogram , which is a graphical representation of Cox proportional hazards model adopting six weighted risk factors including age , CA125 , IP/IV delivery , stage , histology , and upper abdominal metastases . The nomogram was internally vali date d for discrimination and calibration . The concordance index was used for quantifying the predictive ability of overall survival with bootstrapping to correct for bias . RESULTS The cycles of completed IP chemotherapy had an impact on overall survival ( > or = 5 vs. < or = 4 cycles , P=0.02 ) . A nomogram for predicting median survival and 5-year survival probability was constructed with a concordance index of 0.72 . Upper abdominal tumor metastases ( P<0.001 ) and colon resection ( P=0.02 ) predicted increased chances for early discontinuation of IP chemotherapy . CONCLUSIONS At least five IP cycles are needed to achieve better survival . Nomogram can help to identify the subset of patients who can least benefit from IP chemotherapy , thus avoiding potential IP complications and help to facilitate discussion between patient and physician , risk stratification , and help to guide clinical care BACKGROUND Despite considerable improvement in the treatment of advanced ovarian cancer , the optimization of efficacy and tolerability remains an important issue . Therefore , we performed a r and omized , phase III non-inferiority trial comparing paclitaxel plus cisplatin ( PT ) with paclitaxel plus carboplatin ( TC ) in patients with advanced ovarian cancer . METHODS A total of 798 patients with International Federation of Gynecology and Obstetrics stage IIB-IV were r and omly assigned to receive six courses of either PT or TC at 3-week intervals . The primary endpoint was the proportion of patients without progression at 2 years . Secondary endpoints included toxicity , response to treatment , quality of life , and overall and progression-free survival time . Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality -of-life question naire (QLQ)-C30 , version 2.0 . Survival curves were calculated using the Kaplan-Meier method , and hazard ratios were estimated using the Cox proportional hazards model . RESULTS The proportion of patients without progression at 2 years was not statistically significantly different between the two treatment arms ( 40.0 % for PT versus 37.5 % for TC , difference = 2.5 % , one-sided 95 % confidence interval [ CI ] = - infinity to 8.2 % ) . Median progression-free survival time in the TC arm ( 17.2 months , 95 % CI = 15.2 to 19.3 months ) and the PT arm ( 19.1 months , 95 % CI = 16.7 to 21.5 months ) were also not statistically significantly different ; the same was true of median overall survival time ( 43.3 months , 95 % CI = 37.2 to 47.8 months versus 44.1 months , 95 % CI = 40.2 to 49.4 months , for the TC and PT arms , respectively ) . The TC regimen was associated with a higher frequency of hematologic toxicity , but a lower frequency of gastrointestinal and neurologic toxicity , than the PT regimen . Mean global quality -of-life scores at the end of treatment were statistically significantly better in the TC arm than in the PT arm ( 65.25 versus 51.97 , respectively ; difference = -13.28 , 95 % CI = -18.88 to -7.68 ) . CONCLUSION The TC regimen achieved comparable efficacy to the PT regimen but was associated with better tolerability and quality of life , and should , therefore , be considered as an important alternative for st and ard first-line chemotherapy in patients with advanced ovarian cancer See accompanying article on page 91 . The most significant characteristic feature of ovarian cancer is the intraperitoneal spread in its early occurrence . Therefore , it is reasonable to consider the intraperitoneal ( IP ) chemotherapy for this disease entity . The primary concept of IP chemotherapy is to expose the tumor t 
    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: OBJECTIVE Serum CA-125 values have been advocated in the monitoring of ovarian cancer patients receiving intravenous ( IV ) chemotherapy .  This evaluation sought to determine if the CA-125 test can be used to monitor treatment effect among patients receiving intraperitoneal chemotherapy ( IP ) .  METHODS Patient charts from a phase III clinical trial ( GOG 172 ) were retrospectively review ed . Serum CA-125 levels prior to each cycle of therapy were collected and compared between the IV and IP chemotherapy delivery . The association between CA-125 and progression-free survival ( PFS ) or overall survival ( OS ) was estimated and the homogeneity of the results between IP and IV chemotherapy was assessed . RESULTS A total of 177 patients were treated with IV chemotherapy and 165 patients with IP chemotherapy with CA-125 data available were included in this analysis . The observed difference was not statistically significant in median CA-125 levels between the IV and IP arms at any time point ( P>0.05 for all ) . Following surgery and adjuvant chemotherapy , patients with an abnormal CA-125 > 35 U/ml were 2.45 times more likely to have disease progression ( 95 % CI : 1.52 - 3.95 , P<0.001 ) and 2.78 times more likely to die of disease ( 95 % CI : 1.66 - 4.65 , P<0.001 ) , compared to those with a CA-125 < 35 U/ml . These results were consistent with IP and IV chemotherapy . CONCLUSION Serum CA-125 levels decrease in a similar manner during IP chemotherapy when compared to IV chemotherapy . Serum CA-125 algorithms for monitoring treatment effect that have been established for IV chemotherapy may also be applied for patients receiving IP chemotherapy OBJECTIVE To compare the survival between intraperitoneal cisplatin-based chemotherapy ( IPCT ) and intravenous cisplatin-based chemotherapy ( IVCT ) in stage III epithelial ovarian cancer with minimal residual disease ( < 1 cm ) after primary debulking surgery . METHOD One hundred and thirty-two patients with stage III epithelial ovarian cancer after optimal primary debulking surgery with minimal residual disease between April 1990 and March 1995 were entered into a r and omized clinical trial in which IPCT or IVCT was administered at 3-week intervals . Patients in the IPCT arm received cisplatin-based ( 100 mg/m(2 ) ) intraperitoneal chemotherapy . Patients in the IVCT arm received cisplatin-based ( 50 mg/m(2 ) ) intravenous chemotherapy . The tumor response was assessed every 3 months . The hematological toxicity using the South West Oncology Group ( SWOG ) toxicity criteria was assessed . Catheter complications associated with intraperitoneal chemotherapy were also analyzed . RESULT The estimated median survival in the IPCT group was 43 months ( 95 % confidence interval , 34 - 54 ) and IVCT group was 48 months ( 95 % confidence interval , 37 - 59 ) . The hazard ratio of death was not statistically significant between IPCT and IVCT ( hazard ratio , 1.13 ; 95 % CI , 0.69 - 1.86 ; P=0.317 ) . The frequencies of hematological toxic effects were significantly lower in the IPCT group than in the IVCT group . CONCLUSION Intravenous and intraperitoneal chemotherapy are associated with equivalent survival in patients with minimal residual stage III epithelial ovarian cancer after optimal cytoreductive surgery Purpose : To assess the antitumor efficacy and safety of 2 treatment modalities : intraperitoneal carboplatin combined with intravenous ( IV ) paclitaxel . Patients and Methods : Eligible patients were those with epithelial ovarian carcinoma or primary peritoneal carcinoma stages II to IV who underwent initial surgery and had a residual tumor size of 2 cm or larger . Patients received IV paclitaxel 175 mg/m2 followed by intraperitoneal carboplatin AUC6 . The primary end point was a response . Secondary end points were toxicity , progression-free survival , and overall survival . Results : Twenty-six patients were enrolled , and 24 patients were eligible for assessment . The response rate was 83.3 % ( 95 % CI , 62.6%-95.3 % ; Table 4 ) . The median progression-free survival was 25 months . The median overall survival had not been reached . Incidences of grade ( G ) 3/4 hematological toxicities were absolute neutrophil count , 96 % ; hemoglobin , 29 % ; and thrombocytopenia , 16 % . Nonhematological toxicities included G2 liver function , 4 % ; G3 sensory neuropathy , 8 % ; and G3 myalgia and arthralgia , 4 % . Conclusions : Intraperitoneal administration of carboplatin combined with IV paclitaxel was well tolerated and showed satisfactory response in the patients with bulky residual tumor . Large-scale phase III trial comparing with IV carboplatin is warranted in this patient population Summary The currently accepted therapies for ovarian cancer have produced only limited numbers of extended complete remissions in advanced-stage disease . Studies of high-volume intraperitoneal chemotherapy have been initiated to define the toxicology , pharmacokinetics , and the therapeutic effectiveness of this treatment modality . This technique has been virtually ignored until recently , because little success has been achieved with it except in one study ( Rutledge , 1966 ) , in which large intraperitoneal fluid volumes were used . The general lack of success probably reflects inadequate attention to physiologic and pharmacologic principles of drug distribution and absorption in a space as large as the peritoneal cavity . Biomedical engineers , pharmacologists , and clinicians at the NCI have cooperated in the development of a rational chemotherapy for ovarian cancer . Following mathematical pharmacokinetic modeling and toxicologic studies in rat , a Phase I clinical trial of intraperitoneal methotrexate administered in large volumes of dialysis fluid was initiated . Results in three patients confirm the practicality of this approach , and further investigation is warranted A phase III study was conducted comparing intraperitoneal ( ip ) versus intravenous ( iv ) cisplatin-based therapy for patients with newly diagnosed ovarian cancer to determine if the pharmacologic advantage of ip delivery could be translated into an improved response and survival rate .  Twenty-nine patients were r and omized to receive six cycles of ip cisplatin 200 mg/m2 plus ip etoposide 350 mg/m2 with iv thiosulfate protection given every 4 weeks ; thirty-three patients were r and omized to receive six cycles of iv cisplatin 100 mg/m2 plus iv cyclophosphamide 600 mg/m2 administered every 3 weeks . Patients were stratified by stage ( IIC-IV ) and size of residual disease ( > or < or = 1 cm ) . The study was conducted in a community-wide setting . The complete response in evaluable patients was 48 % in the ip group and 52 % in the iv group . The surgical complete response rate for all patients on study , underestimated because not all patients in complete clinical remission had a second-look laparotomy , was 31 % in the ip group and 33 % in the iv group . There was no difference in the response rates between the treatment arms as a function of residual disease < or = or > 1 cm . With a median follow-up of 46 months ( range 21 - 70 months ) there is no difference in response duration or survival . Both regimens were well tolerated with comparable hematologic and nonhematologic toxicity Retrospective studies and a Phase II trial demonstrated the promising efficacy and safety of intraperitoneal administration of carboplatin in ovarian , fallopian tube and primary peritoneal cancer . A Japanese Gynecologic Oncology Group 3016 r and omized Phase III trial for these cancers showed dose-dense weekly administration of paclitaxel significant improvement of progression-free survival and overall survival over every 3-week administration . From June 2010 , we have been conducting a r and omized Phase II/III trial of intravenous versus intraperitoneal administration of carboplatin every 3 week in combination with dose-dense weekly administration of paclitaxel . The purpose of this trial is to prove the superiority of intraperitoneal administration of carboplatin over intravenous administration . Primary endpoint is progression-free survival and secondary endpoints include overall survival , quality of life assessment and cost-benefit .  The first 120 patients will be evaluated for the feasibility of intraperitoneal arm and a total of 746 patients will be enrolled in a Phase III study OBJECTIVE Intraperitoneal ( IP ) chemotherapy has gained enthusiasm in the treatment of ovarian cancer . Despite having a better survival advantage than intravenous ( IV ) chemotherapy , IP chemotherapy still poses significant morbidity and complications . Identifying the subset of patients who could best benefit from IP chemotherapy  , and those who would least benefit from this treatment , thus avoiding potential complications , is critical . METHODS Between January 2001 and December 2007 , 367 patients with stage III epithelial ovarian cancer underwent r and omized trial for IP/IV chemotherapy  were recruited to construct a nomogram , which is a graphical representation of Cox proportional hazards model adopting six weighted risk factors including age , CA125 , IP/IV delivery , stage , histology , and upper abdominal metastases . The nomogram was internally vali date d for discrimination and calibration . The concordance index was used for quantifying the predictive ability of overall survival with bootstrapping to correct for bias . RESULTS The cycles of completed IP chemotherapy had an impact on overall survival ( > or = 5 vs. < or = 4 cycles , P=0.02 ) . A nomogram for predicting median survival and 5-year survival probability was constructed with a concordance index of 0.72 . Upper abdominal tumor metastases ( P<0.001 ) and colon resection ( P=0.02 ) predicted increased chances for early discontinuation of IP chemotherapy . CONCLUSIONS At least five IP cycles are needed to achieve better survival . Nomogram can help to identify the subset of patients who can least benefit from IP chemotherapy , thus avoiding potential IP complications and help to facilitate discussion between patient and physician , risk stratification , and help to guide clinical care BACKGROUND Despite considerable improvement in the treatment of advanced ovarian cancer , the optimization of efficacy and tolerability remains an important issue . Therefore , we performed a r and omized , phase III non-inferiority trial comparing paclitaxel plus cisplatin ( PT ) with paclitaxel plus carboplatin ( TC ) in patients with advanced ovarian cancer . METHODS A total of 798 patients with International Federation of Gynecology and Obstetrics stage IIB-IV were r and omly assigned to receive six courses of either PT or TC at 3-week intervals . The primary endpoint was the proportion of patients without progression at 2 years . Secondary endpoints included toxicity , response to treatment , quality of life , and overall and progression-free survival time . Quality of life was evaluated using the European Organization for Research and Treatment of Cancer quality -of-life question naire (QLQ)-C30 , version 2.0 . Survival curves were calculated using the Kaplan-Meier method , and hazard ratios were estimated using the Cox proportional hazards model . RESULTS The proportion of patients without progression at 2 years was not statistically significantly different between the two treatment arms ( 40.0 % for PT versus 37.5 % for TC , difference = 2.5 % , one-sided 95 % confidence interval [ CI ] = - infinity to 8.2 % ) . Median progression-free survival time in the TC arm ( 17.2 months , 95 % CI = 15.2 to 19.3 months ) and the PT arm ( 19.1 months , 95 % CI = 16.7 to 21.5 months ) were also not statistically significantly different ; the same was true of median overall survival time ( 43.3 months , 95 % CI = 37.2 to 47.8 months versus 44.1 months , 95 % CI = 40.2 to 49.4 months , for the TC and PT arms , respectively ) . The TC regimen was associated with a higher frequency of hematologic toxicity , but a lower frequency of gastrointestinal and neurologic toxicity , than the PT regimen . Mean global quality -of-life scores at the end of treatment were statistically significantly better in the TC arm than in the PT arm ( 65.25 versus 51.97 , respectively ; difference = -13.28 , 95 % CI = -18.88 to -7.68 ) . CONCLUSION The TC regimen achieved comparable efficacy to the PT regimen but was associated with better tolerability and quality of life , and should , therefore , be considered as an important alternative for st and ard first-line chemotherapy in patients with advanced ovarian cancer See accompanying article on page 91 . The most significant characteristic feature of ovarian cancer is the intraperitoneal spread in its early occurrence . Therefore , it is reasonable to consider the intraperitoneal ( IP ) chemotherapy for this disease entity . The primary concept of IP chemotherapy is to expose the tumor t 
    Output:
    