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: A r and omised phase III trial was conducted to assess the role of interferon-alpha ( INFα ) 2a as maintenance therapy following surgery and /or chemotherapy in patients with epithelial ovarian carcinoma . Patients were r and omised following initial surgery/chemotherapy to interferon-alpha 2a as 4.5 mega-units subcutaneously 3 days per week or to no further treatment . A total of 300 patients were r and omised within the study between February 1990 and July 1997 . No benefit for interferon maintenance was seen in terms of either overall or clinical event-free survival . We conclude that INF-α is not effective as a maintenance therapy in the management of women with ovarian cancer . The need for novel therapeutics or strategies to prevent the almost inevitable relapse of patients despite increasingly effective surgery and chemotherapy remains Intraperitoneal treatment with interferon-γ ( IFN-γ ) has been shown to achieve surgically documented responses in the second-line therapy of ovarian cancer . To assess its efficacy in the first-line therapy , we conducted a r and omized controlled trial with 148 patients who had undergone primary surgery for FIGO stage Ic – IIIc ovarian cancer . In the control arm women received 100 mg m–2cisplatin and 600 mg m–2cyclophosphamide , the experimental arm included the above regimen with IFN-γ 0.1 mg subcutaneously on days 1 , 3 , 5 , 15 , 17 and 19 of each 28-day cycle . Progression-free survival at 3 years was improved from 38 % in controls to 51 % in the treatment group corresponding to median times to progression of 17 and 48 months ( P = 0.031 , relative risk of progression 0.48 , confidence interval 0.28–0.82 ) . Three-year overall survival was 58 % and 74 % accordingly ( n.s . , median not yet reached ) . Complete clinical responses were observed in 68 % with IFN-γ versus 56 % in controls ( n.s . ) . Toxicity was comparable in both groups except for a mild flu-like syndrome , experienced by most patients after administration of IFN-γ . Thus , with acceptable toxicity , the inclusion of IFN-γ in the first-line chemotherapy of ovarian cancer yielded a benefit in prolonging progression-free survival . © 2000 Cancer Research Twenty-four patients with advanced and therapy-resistant ovarian carcinoma were treated with escalating daily doses of human leukocyte interferon ( IFN ) . Doses ranged from 3 X 106 to 27 X 106 IU/day . Fatigue , fever , thrombocytopenia , and leukopenia were the limiting factors in the escalation of doses . Of nine patients treated for at least 2 months , there were two patients with partial remissions and six with stable disease . Ascites production present in four patients became reduced in three . The level of 2',5'-oligoadenylate synthetase in peripheral blood lymphocytes increased following initiation of IFN therapy . We conclude that IFN-α can exert an anti-tumor effect in some patients with ovarian carcinoma that have previously failed on other therapy regimens The use of interferon for the induction treatment of multiple myeloma has been shown to be effective in about 20 percent of patients . We studied its effects on long-term survival when it was used for maintenance treatment . Between April 1985 and May 1988 , 101 patients with symptomatic multiple myeloma who had had a substantial objective response or a lesser objective response with disappearance of symptoms ( " disease stabilization " ) after 12 courses of induction chemotherapy were r and omly assigned to receive recombinant interferon alfa-2b as maintenance therapy ( n = 50 ) or to receive no treatment ( n = 51 ) . As of December 1989 , 66 of the 101 patients have relapsed ( 25 given interferon and 41 not treated ) . The median duration of response ( from the time of r and omization ) was 26 months in the patients given interferon and 14 months in the untreated patients ( P = 0.0002 ) . A total of 37 patients have died ( 14 given interferon and 23 not treated ) . The median duration of survival ( from r and omization ) was 52 months in the interferon group and 39 months in the control group ( P = 0.0526 ) . Among the patients who had had a substantial objective response to induction chemotherapy , the difference in survival time was statistically significant ( P = 0.03526 ) . Interferon had to be stopped because of toxic effects in 3 of 12 patients initially treated with 10 MU ( megaunits ) per square meter of body-surface area . After the dose was reduced to 3 MU per square meter , the only toxic effect was a mild influenza-like syndrome lasting two to three weeks . We conclude that maintenance treatment with interferon prolongs response and survival in patients with multiple myeloma who have responded to conventional induction chemotherapy In a prospect i ve r and omized trial , consolidation treatment with radiotherapy or chemotherapy was compared with no treatment in a series of 172 patients with epithelial ovarian carcinoma , FIGO stage III , with complete surgical remission after primary cytoreductive surgery and induction chemotherapy .  In the subgroup with complete surgical and pathologic remission , progression-free survival was significantly ( P = 0.032 ) better in the radiotherapy group ( 56 % at 5 years ) than in the chemotherapy group ( 36 % at 5 years ) and the untreated control group ( 35 % at 5 years ) . Overall survival was also most favorable in the radiotherapy group ( 69 % at 5 years ) . The number of recurrences was lowest in the radiotherapy group . In the subgroup with microscopic residual carcinoma there were no significant differences in survival between the radiotherapy and the chemotherapy-treated patients . Early and late radiation reactions were recorded . Treatment-related side effects were seen most frequently in the radiotherapy group . Late intestinal radiation reactions of a severe type were recorded in 10 % A phase II study was initiated in March 1987 at the Regina Elena National Cancer Institute of Rome to evaluate the efficacy of alternating intraperitoneal ( IP ) recombinant alpha-2-interferon ( r-alpha 2-IFN ) and cisplatin ( DDP ) as salvage therapy for less than or equal to 5 mm residual-disease ( RD ) ovarian carcinoma . Fourteen assessable patients entered the study . All had received prior chemotherapy ( 11 with DDP-based regimens ) ; five patients had macroscopic RD ( less than or equal to 5 mm ) , and nine had microscopic RD ( histologically positive r and om biopsies and /or positive cytology and immunocytochemical tests ) . The response to IP immunochemotherapy was evaluated by laparotomy .  Pathologic complete remissions ( PCRs ) were achieved in seven patients ( 50 % ) who have remained free of disease with a median follow-up of 22 + months ( range , 11 + to 30 + months ) . Six patients achieved a stable disease and one presented disease progression . With the exception of chemical peritonitis-induced adhesions , no limiting toxicity was observed . The results obtained in this small , highly selected series demonstrate that a high PCR rate may be obtained with IP immunochemotherapy with DDP and r-alpha 2-IFN as salvage therapy in residual ovarian carcinoma less than or equal to 5 mm after first-line chemotherapy also including intravenous ( IV ) DDP . Larger comparative studies must be conducted to establish the potential role of IP  DDP and r-alpha 2-IFN  as compared with either of the single treatments OBJECTIVE Despite the improvement in progression-free and overall survival in patients with advanced ovarian cancer associated with platinum-taxane chemotherapy , strategies are needed to prevent the greater than 70 % recurrence rate . METHOD The Southwest Oncology Group ( SWOG ) initiated a phase III intergroup trial of alpha-interferon ( IFNalpha-26 , Schering-Plough , Kenilworth , NJ ) in weekly doses of 50 x 10(6 ) IU ( for 6 doses ) versus observation only in patients with no pathological evidence of residual disease at second-look surgery in 1988 . RESULTS Patient accrual was extremely slow and the trial was permanently closed in 1999 by the SWOG Data and Safety Monitoring Committee with 74 registered patients . Of these patients , 70 were evaluable for progression-free and overall survival .  There was no significant difference between the two study arms in relation to median progression-free survival ( P = 0.56 ) . The median survival duration associated with intraperitoneal alpha-interferon had not been reached versus 87 months on the observation arm . In general , intraperitoneal alpha-interferon was well tolerated . There were no treatment-related deaths or grade 4 adverse events . Although no efficacy conclusions can be drawn from this prematurely closed trial , it should be noted that 57 % of the patients on the observation arm recurred and all died , whereas 63 % recurred and only 43 % died on the intraperitoneal alpha-interferon arm . CONCLUSION Although this was a negative study , there should continue to be interest in the use of biological therapy to improve survival of patients in complete remission following primary chemotherapy OBJECTIVES Interferon gamma ( IFN-gamma ) is a pleiotropic cytokine with antiproliferative , immunostimulatory , and chemosensitization properties . This trial was design ed to evaluate IFN-gamma 1b plus carboplatin and paclitaxel in treatment-naive ovarian cancer ( OC ) and primary peritoneal carcinoma ( PPC ) patients . METHODS Eligible patients were r and omized to 6 cycles of carboplatin/paclitaxel every 3 weeks or the same in combination with IFN-gamma 1b ( 100 microg 3x/wk subcutaneously ) . The primary endpoint was overall survival ( OS ) time ( target hazard ratio (HR)=0.77 ) . Secondary endpoints included progression-free survival ( target HR=0.7 ) , based on blinded review of serial imaging scans , physical exams , and CA-125 levels . RESULTS 847 patients were enrolled ( OC 774 , PPC 73 ) in Europe ( n=539 ) and North/South America ( n=308 ) from January 29 , 2002 to March 31 , 2004 and stratified according to : optimal debulking ( n=271 ) versus suboptimal debulking with plans for interval debulking ( PID ) ( n=238 ) or no PID ( n=338 ) . The study stopped early following a protocol -defined second interim analysis which revealed significantly shorter OS time in patients receiving IFN-gamma 1b plus chemotherapy compared to chemotherapy alone ( 1138 days vs. not estimable , HR=1.45 , 95 % CI=1.15 - 1.83 ) . At the time of the analysis , 169 of 426 ( 39.7 % ) patients in the IFN-gamma 1b plus chemotherapy group had died compared to 128 of 421 ( 30.4 % ) in the chemotherapy alone group . Serious adverse events were more common in the IFN-gamma 1b plus chemotherapy group ( 48.5 % vs. 35.4 % ) , primarily due to a higher incidence of serious hematological toxicities ( 34.5 % vs. 22.7 % ) . CONCLUSIONS Treatment with IFN-gamma 1b in combination with carboplatin/paclitaxel does not have a role in the first-line treatment of advanced ovarian cancer OBJECTIVE The aim of the study was to evaluate the effect of additional radiotherapy after chemotherapy on the relapse-free and overall survival rates of patients with advanced ovarian cancer . METHODS Between 1985 and 1992 64 patients with radically operated ovarian cancers ( 4 stage IC , 2 stage II , 54 stage III , and 4 stage IV ) were enrolled in a r and omized study . Radical surgery comprised total abdominal hysterectomy and bilateral salpingo-oophorectomy , omentectomy , and pelvic and paraaortic lymphadenectomy . All patients received adjuvant chemotherapy with carboplatin IV 400 mg/m2 , epirubicin IV 70 mg/m2 on day 1 and prednimustine orally 100 mg/m2 on days 3 to 7 at 1-month intervals . Thirty-two patients without residual disease were r and omized to whole abdominal radiation ( 30 Gy , administered over 4 weeks ) . An additional 21.6 Gy were delivered to the pelvis and 12 Gy to the paraaortic region up to the diaphragm for total doses of 51.6 and 42 Gy , respectively . Cancer-related survival was calculated with the Kaplan-Meier and Cox proportional hazards methods . RESULTS The relapse-free and overall survival rates of patients who received adjuvant chemoradiotherapy were significantly higher than those of patients who received adjuvant chemotherapy only ( 68 % vs 56 % at 2 years and 49 % vs 26 % at 5 years , P = 0.013 , and 87 % vs 61 % at 2 years and 59 % vs 33 % at 5 years , 
    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: A r and omised phase III trial was conducted to assess the role of interferon-alpha ( INFα ) 2a as maintenance therapy following surgery and /or chemotherapy in patients with epithelial ovarian carcinoma . Patients were r and omised following initial surgery/chemotherapy to interferon-alpha 2a as 4.5 mega-units subcutaneously 3 days per week or to no further treatment . A total of 300 patients were r and omised within the study between February 1990 and July 1997 . No benefit for interferon maintenance was seen in terms of either overall or clinical event-free survival . We conclude that INF-α is not effective as a maintenance therapy in the management of women with ovarian cancer . The need for novel therapeutics or strategies to prevent the almost inevitable relapse of patients despite increasingly effective surgery and chemotherapy remains Intraperitoneal treatment with interferon-γ ( IFN-γ ) has been shown to achieve surgically documented responses in the second-line therapy of ovarian cancer . To assess its efficacy in the first-line therapy , we conducted a r and omized controlled trial with 148 patients who had undergone primary surgery for FIGO stage Ic – IIIc ovarian cancer . In the control arm women received 100 mg m–2cisplatin and 600 mg m–2cyclophosphamide , the experimental arm included the above regimen with IFN-γ 0.1 mg subcutaneously on days 1 , 3 , 5 , 15 , 17 and 19 of each 28-day cycle . Progression-free survival at 3 years was improved from 38 % in controls to 51 % in the treatment group corresponding to median times to progression of 17 and 48 months ( P = 0.031 , relative risk of progression 0.48 , confidence interval 0.28–0.82 ) . Three-year overall survival was 58 % and 74 % accordingly ( n.s . , median not yet reached ) . Complete clinical responses were observed in 68 % with IFN-γ versus 56 % in controls ( n.s . ) . Toxicity was comparable in both groups except for a mild flu-like syndrome , experienced by most patients after administration of IFN-γ . Thus , with acceptable toxicity , the inclusion of IFN-γ in the first-line chemotherapy of ovarian cancer yielded a benefit in prolonging progression-free survival . © 2000 Cancer Research Twenty-four patients with advanced and therapy-resistant ovarian carcinoma were treated with escalating daily doses of human leukocyte interferon ( IFN ) . Doses ranged from 3 X 106 to 27 X 106 IU/day . Fatigue , fever , thrombocytopenia , and leukopenia were the limiting factors in the escalation of doses . Of nine patients treated for at least 2 months , there were two patients with partial remissions and six with stable disease . Ascites production present in four patients became reduced in three . The level of 2',5'-oligoadenylate synthetase in peripheral blood lymphocytes increased following initiation of IFN therapy . We conclude that IFN-α can exert an anti-tumor effect in some patients with ovarian carcinoma that have previously failed on other therapy regimens The use of interferon for the induction treatment of multiple myeloma has been shown to be effective in about 20 percent of patients . We studied its effects on long-term survival when it was used for maintenance treatment . Between April 1985 and May 1988 , 101 patients with symptomatic multiple myeloma who had had a substantial objective response or a lesser objective response with disappearance of symptoms ( " disease stabilization " ) after 12 courses of induction chemotherapy were r and omly assigned to receive recombinant interferon alfa-2b as maintenance therapy ( n = 50 ) or to receive no treatment ( n = 51 ) . As of December 1989 , 66 of the 101 patients have relapsed ( 25 given interferon and 41 not treated ) . The median duration of response ( from the time of r and omization ) was 26 months in the patients given interferon and 14 months in the untreated patients ( P = 0.0002 ) . A total of 37 patients have died ( 14 given interferon and 23 not treated ) . The median duration of survival ( from r and omization ) was 52 months in the interferon group and 39 months in the control group ( P = 0.0526 ) . Among the patients who had had a substantial objective response to induction chemotherapy , the difference in survival time was statistically significant ( P = 0.03526 ) . Interferon had to be stopped because of toxic effects in 3 of 12 patients initially treated with 10 MU ( megaunits ) per square meter of body-surface area . After the dose was reduced to 3 MU per square meter , the only toxic effect was a mild influenza-like syndrome lasting two to three weeks . We conclude that maintenance treatment with interferon prolongs response and survival in patients with multiple myeloma who have responded to conventional induction chemotherapy In a prospect i ve r and omized trial , consolidation treatment with radiotherapy or chemotherapy was compared with no treatment in a series of 172 patients with epithelial ovarian carcinoma , FIGO stage III , with complete surgical remission after primary cytoreductive surgery and induction chemotherapy .  In the subgroup with complete surgical and pathologic remission , progression-free survival was significantly ( P = 0.032 ) better in the radiotherapy group ( 56 % at 5 years ) than in the chemotherapy group ( 36 % at 5 years ) and the untreated control group ( 35 % at 5 years ) . Overall survival was also most favorable in the radiotherapy group ( 69 % at 5 years ) . The number of recurrences was lowest in the radiotherapy group . In the subgroup with microscopic residual carcinoma there were no significant differences in survival between the radiotherapy and the chemotherapy-treated patients . Early and late radiation reactions were recorded . Treatment-related side effects were seen most frequently in the radiotherapy group . Late intestinal radiation reactions of a severe type were recorded in 10 % A phase II study was initiated in March 1987 at the Regina Elena National Cancer Institute of Rome to evaluate the efficacy of alternating intraperitoneal ( IP ) recombinant alpha-2-interferon ( r-alpha 2-IFN ) and cisplatin ( DDP ) as salvage therapy for less than or equal to 5 mm residual-disease ( RD ) ovarian carcinoma . Fourteen assessable patients entered the study . All had received prior chemotherapy ( 11 with DDP-based regimens ) ; five patients had macroscopic RD ( less than or equal to 5 mm ) , and nine had microscopic RD ( histologically positive r and om biopsies and /or positive cytology and immunocytochemical tests ) . The response to IP immunochemotherapy was evaluated by laparotomy .  Pathologic complete remissions ( PCRs ) were achieved in seven patients ( 50 % ) who have remained free of disease with a median follow-up of 22 + months ( range , 11 + to 30 + months ) . Six patients achieved a stable disease and one presented disease progression . With the exception of chemical peritonitis-induced adhesions , no limiting toxicity was observed . The results obtained in this small , highly selected series demonstrate that a high PCR rate may be obtained with IP immunochemotherapy with DDP and r-alpha 2-IFN as salvage therapy in residual ovarian carcinoma less than or equal to 5 mm after first-line chemotherapy also including intravenous ( IV ) DDP . Larger comparative studies must be conducted to establish the potential role of IP  DDP and r-alpha 2-IFN  as compared with either of the single treatments OBJECTIVE Despite the improvement in progression-free and overall survival in patients with advanced ovarian cancer associated with platinum-taxane chemotherapy , strategies are needed to prevent the greater than 70 % recurrence rate . METHOD The Southwest Oncology Group ( SWOG ) initiated a phase III intergroup trial of alpha-interferon ( IFNalpha-26 , Schering-Plough , Kenilworth , NJ ) in weekly doses of 50 x 10(6 ) IU ( for 6 doses ) versus observation only in patients with no pathological evidence of residual disease at second-look surgery in 1988 . RESULTS Patient accrual was extremely slow and the trial was permanently closed in 1999 by the SWOG Data and Safety Monitoring Committee with 74 registered patients . Of these patients , 70 were evaluable for progression-free and overall survival .  There was no significant difference between the two study arms in relation to median progression-free survival ( P = 0.56 ) . The median survival duration associated with intraperitoneal alpha-interferon had not been reached versus 87 months on the observation arm . In general , intraperitoneal alpha-interferon was well tolerated . There were no treatment-related deaths or grade 4 adverse events . Although no efficacy conclusions can be drawn from this prematurely closed trial , it should be noted that 57 % of the patients on the observation arm recurred and all died , whereas 63 % recurred and only 43 % died on the intraperitoneal alpha-interferon arm . CONCLUSION Although this was a negative study , there should continue to be interest in the use of biological therapy to improve survival of patients in complete remission following primary chemotherapy OBJECTIVES Interferon gamma ( IFN-gamma ) is a pleiotropic cytokine with antiproliferative , immunostimulatory , and chemosensitization properties . This trial was design ed to evaluate IFN-gamma 1b plus carboplatin and paclitaxel in treatment-naive ovarian cancer ( OC ) and primary peritoneal carcinoma ( PPC ) patients . METHODS Eligible patients were r and omized to 6 cycles of carboplatin/paclitaxel every 3 weeks or the same in combination with IFN-gamma 1b ( 100 microg 3x/wk subcutaneously ) . The primary endpoint was overall survival ( OS ) time ( target hazard ratio (HR)=0.77 ) . Secondary endpoints included progression-free survival ( target HR=0.7 ) , based on blinded review of serial imaging scans , physical exams , and CA-125 levels . RESULTS 847 patients were enrolled ( OC 774 , PPC 73 ) in Europe ( n=539 ) and North/South America ( n=308 ) from January 29 , 2002 to March 31 , 2004 and stratified according to : optimal debulking ( n=271 ) versus suboptimal debulking with plans for interval debulking ( PID ) ( n=238 ) or no PID ( n=338 ) . The study stopped early following a protocol -defined second interim analysis which revealed significantly shorter OS time in patients receiving IFN-gamma 1b plus chemotherapy compared to chemotherapy alone ( 1138 days vs. not estimable , HR=1.45 , 95 % CI=1.15 - 1.83 ) . At the time of the analysis , 169 of 426 ( 39.7 % ) patients in the IFN-gamma 1b plus chemotherapy group had died compared to 128 of 421 ( 30.4 % ) in the chemotherapy alone group . Serious adverse events were more common in the IFN-gamma 1b plus chemotherapy group ( 48.5 % vs. 35.4 % ) , primarily due to a higher incidence of serious hematological toxicities ( 34.5 % vs. 22.7 % ) . CONCLUSIONS Treatment with IFN-gamma 1b in combination with carboplatin/paclitaxel does not have a role in the first-line treatment of advanced ovarian cancer OBJECTIVE The aim of the study was to evaluate the effect of additional radiotherapy after chemotherapy on the relapse-free and overall survival rates of patients with advanced ovarian cancer . METHODS Between 1985 and 1992 64 patients with radically operated ovarian cancers ( 4 stage IC , 2 stage II , 54 stage III , and 4 stage IV ) were enrolled in a r and omized study . Radical surgery comprised total abdominal hysterectomy and bilateral salpingo-oophorectomy , omentectomy , and pelvic and paraaortic lymphadenectomy . All patients received adjuvant chemotherapy with carboplatin IV 400 mg/m2 , epirubicin IV 70 mg/m2 on day 1 and prednimustine orally 100 mg/m2 on days 3 to 7 at 1-month intervals . Thirty-two patients without residual disease were r and omized to whole abdominal radiation ( 30 Gy , administered over 4 weeks ) . An additional 21.6 Gy were delivered to the pelvis and 12 Gy to the paraaortic region up to the diaphragm for total doses of 51.6 and 42 Gy , respectively . Cancer-related survival was calculated with the Kaplan-Meier and Cox proportional hazards methods . RESULTS The relapse-free and overall survival rates of patients who received adjuvant chemoradiotherapy were significantly higher than those of patients who received adjuvant chemotherapy only ( 68 % vs 56 % at 2 years and 49 % vs 26 % at 5 years , P = 0.013 , and 87 % vs 61 % at 2 years and 59 % vs 33 % at 5 years , 
    Output:
    