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: OBJECTIVES To evaluate the effect of adjuvant thalidomide on recurrence-free survival ( RFS ) after nephrectomy for high-risk metastatic renal cell carcinoma ( RCC ) . METHODS Eligibility criteria for enrollment on this r and omized trial included any histologic subtype , T2 ( high grade , any N ) , T3/T4 ( any grade , any N ) , or node-positive ( any grade , any T ) RCC . We r and omized eligible patients to observation or to receive thalidomide 300 mg daily for 24 months . Patients were observed until disease recurrence or death . RESULTS After we enrolled 46 patients , we stopped the trial at a median follow up of 43.9 months ( range , 9.7 - 74.2 months ) . Patients on the thalidomide arm had inferior 2- and 3-year probabilities of RFS , compared with controls ( 47.8 % vs 69.3 % and 28.7 % vs 69.3 % , respectively ; P = .022 ) . The 2- and 3-year cancer-specific survival was similar for both groups . All observed deaths were attributable to RCC ( P = .392 ) . By multivariate analysis , tumor size and grade predicted recurrence ( P = .001 and .013 ) and kidney cancer-specific death ( P = .002 and .014 ) . Thalidomide treatment , however , was not an independent predictor of recurrence or cancer-specific mortality . CONCLUSIONS In this small , r and omized , controlled trial , adjuvant thalidomide therapy after complete resection of high-risk RCC did not improve the 2- and 3-year RFS rates or cancer-specific death rates BACKGROUND Organ-confined renal-cell carcinoma is associated with tumour progression in up to 50 % of patients after radical nephrectomy . At present , no effective adjuvant treatment is established . We aim ed to investigate the effect of an autologous renal tumour cell vaccine on risk of tumour progression in patients with stage pT2 - 3b pN0 - 3 M0 renal-cell carcinoma . METHODS Between January , 1997 , and September , 1998 , 558 patients with a renal tumour scheduled for radical nephrectomy were enrolled at 55 institutions in Germany . Before surgery , all patients were central ly r and omised to receive autologous renal tumour cell vaccine ( six intradermal applications at 4-week intervals postoperatively ; vaccine group ) or no adjuvant treatment ( control group ) . The primary endpoint of the trial was to reduce the risk of tumour progression , defined as progression or death . All patients were assessed after st and ardised diagnostic investigations at 6-month intervals for a minimum of 4.5 years . FINDINGS By preoperative and postoperative inclusion criteria , 379 patients were assessable for the intention-to-treat analysis . At 5-year and 70-month follow-up , the hazard ratios for tumour progression were 1.58 ( 95 % CI 1.05 - 2.37 ) and 1.59 ( 1.07 - 2.36 ) , respectively , in favour of the vaccine group ( p=0.0204 , log-rank test ) . 5-year and 70-month progression-free survival rates were 77.4 % and 72 % , respectively , in the vaccine group and 67.8 % and 59.3 % , respectively , in the control group . The vaccine was well tolerated , with only 12 adverse events associated with the treatment . INTERPRETATION Adjuvant treatment with autologous renal tumour cell vaccine in patients with renal-cell carcinoma after radical nephrectomy seems to be beneficial and can be considered in patients undergoing radical nephrectomy due to organ-confined renal-cell carcinoma of more than 2.5 cm in diameter We conducted a prospect ively r and omised clinical trial to investigate the role of adjuvant outpatient immunochemotherapy administered postoperatively in high-risk patients with renal cell carcinoma . In total , 203 renal carcinoma patients ' status post radical tumour nephrectomy were stratified into three risk groups : patients with tumour extending into renal vein/vena cava or invading beyond Gerota 's fascia ( pT3b/c pN0 or pT4pN0 ) , patients with locoregional lymph node infiltration ( pN+ ) , and patients after complete resection of tumour relapse or solitary metastasis ( R0 ) . Patients were r and omised to undergo either ( A ) 8 weeks of outpatient subcutaneous interleukin-2 ( sc-rIL-2 ) , subcutaneous interferon-alpha2a ( sc-rIFN-α2a ) , and intravenous 5-fluorouracil ( iv-5-FU ) according to the st and ard Atzpodien regimen ( Atzpodien et al , 2004 ) or ( B ) observation . Two- , 5- , and 8-year survival rates were 81 , 58 , and 58 % in the treatment arm , and 91 , 76 , and 66 % in the observation arm ( log rank P=0.0278 ) , with a median follow-up of 4.3 years . Two , 5- , and 8-year relapse-free survival rates were calculated at 54 , 42 , and 39 % in the treatment arm , and at 62 , 49 , and 49 % in the observation arm ( log rank P=0.2398 ) . Stage-adapted subanalyses revealed no survival advantages of treatment over observation , as well . Our results established that there was no relapse-free survival benefit and the overall survival was inferior with an adjuvant 8-week-outpatient sc-rIL-2/sc-rIFN-α2a/iv-5-FU-based immunochemotherapy compared to observation in high-risk renal cell carcinoma patients following radical tumour nephrectomy PURPOSE Because interferon gave promising results in the management of metastatic renal cell carcinoma in the 1980s , a multicentric r and omized controlled trial was planned to compare adjuvant recombinant interferon alfa-2b ( rIFNalpha2b ) with observation after radical nephrectomy in patients with Robson stages II and III renal cell carcinoma .  Overall and event-free survival were to be evaluated together with prognostic factors . PATIENTS AND METHODS  Overall and event-free survival curves for 247 patients ( 124 controls and 123 treated ) were estimated by the Kaplan-Meier method and compared using the log-rank test . Cox 's multiple regression models were adopted to perform a joint analysis of treatment and prognostic factors . RESULTS The 5-year overall and event-free survival probabilities were 0.665 and 0.671 , respectively , for controls and 0.660 and 0.567 , respectively , for the treated group ; the differences were not statistically significant ( 2P = .861 for overall and 2P = .107 for event-free survival with the log-rank test ) . Regarding prognostic factors , only grade , pT , and pN demonstrated a significant prognostic role . First-order interactions of treatment with pT and pN category were investigated ; a significant interaction was found between pN and treatment . A harmful effect of rIFNalpha2b in the 97 treated pN0 patients and a protective effect in the 13 treated pN2/pN3 patients were statistically significant . CONCLUSION Adjuvant rIFNalpha2b is not indicated after radical nephrectomy for renal cell carcinoma . The protective effect in the small group of pN2/pN3 patients requires further investigation Active specific immunotherapy ( ASI ) is a strategy that attempts to boost the host 's immune response specifically against its own tumor . The purpose of this study was to investigate the effect of adjuvant ASI in patients with renal carcinoma PURPOSE This prospect i ve , r and omized , controlled phase III trial assessed high-dose bolus interleukin-2 ( IL-2 ) postoperatively in patients with high-risk renal cell carcinoma ( RCC ) . PATIENTS AND METHODS Eligibility requirements were resected locally advanced ( LA ; T3b-4 or N1 - 3 ) or metastatic ( M1 ) RCC , no prior systemic therapy , and excellent organ function . R and omized assignment was to one course of IL-2 ( 600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 [ maximum 28 doses ] ) or observation . The study was design ed and powered to show an improvement in predicted 2-year disease-free survival ( DFS ) from 40 % for the observation group to 70 % for the treatment group . The accrual goal was 68 patients with LA disease , with 34 patients per treatment arm . Metastasectomy patients were to be analyzed separately because of their unpredictable natural history . RESULTS Sixty-nine patients were enrolled onto the study ( 44 LA and 25 M1 patients ) .  Toxic effects of IL-2 were as anticipated ; no unexpected serious adverse events or treatment-related deaths occurred . Early closure occurred when an interim analysis determined that the 30 % improvement in 2-year DFS could not be achieved despite full accrual . Sixteen of 21 LA patients receiving IL-2 experienced relapse , compared with 15 of 23 patients in the observation arm ( P = .73 ) ; in the LA group , three deaths occurred in the IL-2 arm , and five deaths occurred in the observation arm ( P = .38 ) . Analysis including metastasectomy patients made no difference in DFS or overall survival . CONCLUSION One course of high-dose bolus IL-2 , though feasible , did not produce the ambitious clinical ly meaningful benefit anticipated when administered postoperatively to patients with resected high-risk RCC PURPOSE To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma . PATIENTS AND METHODS A total of 283 eligible patients with pT3 - 4a and /or node-positive disease were r and omly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL ( Wellferon , Burroughs-Wellcome , Research Park , NC ) given daily for 5 days every 3 weeks for up to 12 cycles . Patients were stratified on the basis of pathologic stage . Patients remained on treatment until documented recurrence , excessive toxicity , or patient/physician preference deemed removal appropriate . RESULTS At median follow-up of 10.4 years , median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm ( log-rank P = .09 ) . Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm ( P = .33 ) . Performance status ( P = .003 ) , nodal status ( N2 v N0 , P < .0001 ) , and tumor stage ( P = .0002 ) were significant prognostic factors in multivariate analysis . A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that r and om assignment to interferon treatment ( P = .009 ) and shorter time to recurrence ( P < .0001 ) were independent predictors of shorter survival after recurrence . Although no lethal toxicities were observed , severe ( grade 4 ) toxicities including neutropenia , myalgia , fatigue , depression , and other neurologic toxicities occurred in 11.4 % of those r and omly assigned to interferon treatment . CONCLUSION Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients PURPOSE To up date response duration and survival data for patients with metastatic renal cell carcinoma treated with high-dose interleukin (IL)-2 .  PATIENTS AND METHODS Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials . Recombinant IL-2 600,000 or 720,000 IU/kg was administered by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinical ly tolerated with maximal support . A second , identical cycle of treatment was scheduled following 5 to 9 days of rest , and courses could be repeated every 6 to 12 weeks in stable or responding patients . All data were up date d as of December 1998 , with report forms completed by the clinical investigators . These data had last been up date d as part of the Food and Drug Administration reporting requirements in 1996 . RESULTS Objective responses previously have been reported in 37 of 255 patients ( 15 % ) with 17 complete responses ( 7 % ) and 20 partial responses ( 8 % ) . These data remain unchanged from previous reports . Median response duration for all objective responders remains unchanged at 54 months , but the range now extends from 3 to > 131 months . Median duration for all complete responses has not yet been reached , but was at least 80 months ( range , 7- > 131 mo ) at the time of this analysis . Median duration for all partial responses remains 20 months ( range , 3- > 126 mo ) . Median survival time for all 255 patients remains 16.3 months , with 10 % to 20 % of patients estimated to be alive 5 to 10 years after treatment with high-dose IL-2 . CONCLUSION With prolonged follow-up , treatment with high-dose recom 
    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: OBJECTIVES To evaluate the effect of adjuvant thalidomide on recurrence-free survival ( RFS ) after nephrectomy for high-risk metastatic renal cell carcinoma ( RCC ) . METHODS Eligibility criteria for enrollment on this r and omized trial included any histologic subtype , T2 ( high grade , any N ) , T3/T4 ( any grade , any N ) , or node-positive ( any grade , any T ) RCC . We r and omized eligible patients to observation or to receive thalidomide 300 mg daily for 24 months . Patients were observed until disease recurrence or death . RESULTS After we enrolled 46 patients , we stopped the trial at a median follow up of 43.9 months ( range , 9.7 - 74.2 months ) . Patients on the thalidomide arm had inferior 2- and 3-year probabilities of RFS , compared with controls ( 47.8 % vs 69.3 % and 28.7 % vs 69.3 % , respectively ; P = .022 ) . The 2- and 3-year cancer-specific survival was similar for both groups . All observed deaths were attributable to RCC ( P = .392 ) . By multivariate analysis , tumor size and grade predicted recurrence ( P = .001 and .013 ) and kidney cancer-specific death ( P = .002 and .014 ) . Thalidomide treatment , however , was not an independent predictor of recurrence or cancer-specific mortality . CONCLUSIONS In this small , r and omized , controlled trial , adjuvant thalidomide therapy after complete resection of high-risk RCC did not improve the 2- and 3-year RFS rates or cancer-specific death rates BACKGROUND Organ-confined renal-cell carcinoma is associated with tumour progression in up to 50 % of patients after radical nephrectomy . At present , no effective adjuvant treatment is established . We aim ed to investigate the effect of an autologous renal tumour cell vaccine on risk of tumour progression in patients with stage pT2 - 3b pN0 - 3 M0 renal-cell carcinoma . METHODS Between January , 1997 , and September , 1998 , 558 patients with a renal tumour scheduled for radical nephrectomy were enrolled at 55 institutions in Germany . Before surgery , all patients were central ly r and omised to receive autologous renal tumour cell vaccine ( six intradermal applications at 4-week intervals postoperatively ; vaccine group ) or no adjuvant treatment ( control group ) . The primary endpoint of the trial was to reduce the risk of tumour progression , defined as progression or death . All patients were assessed after st and ardised diagnostic investigations at 6-month intervals for a minimum of 4.5 years . FINDINGS By preoperative and postoperative inclusion criteria , 379 patients were assessable for the intention-to-treat analysis . At 5-year and 70-month follow-up , the hazard ratios for tumour progression were 1.58 ( 95 % CI 1.05 - 2.37 ) and 1.59 ( 1.07 - 2.36 ) , respectively , in favour of the vaccine group ( p=0.0204 , log-rank test ) . 5-year and 70-month progression-free survival rates were 77.4 % and 72 % , respectively , in the vaccine group and 67.8 % and 59.3 % , respectively , in the control group . The vaccine was well tolerated , with only 12 adverse events associated with the treatment . INTERPRETATION Adjuvant treatment with autologous renal tumour cell vaccine in patients with renal-cell carcinoma after radical nephrectomy seems to be beneficial and can be considered in patients undergoing radical nephrectomy due to organ-confined renal-cell carcinoma of more than 2.5 cm in diameter We conducted a prospect ively r and omised clinical trial to investigate the role of adjuvant outpatient immunochemotherapy administered postoperatively in high-risk patients with renal cell carcinoma . In total , 203 renal carcinoma patients ' status post radical tumour nephrectomy were stratified into three risk groups : patients with tumour extending into renal vein/vena cava or invading beyond Gerota 's fascia ( pT3b/c pN0 or pT4pN0 ) , patients with locoregional lymph node infiltration ( pN+ ) , and patients after complete resection of tumour relapse or solitary metastasis ( R0 ) . Patients were r and omised to undergo either ( A ) 8 weeks of outpatient subcutaneous interleukin-2 ( sc-rIL-2 ) , subcutaneous interferon-alpha2a ( sc-rIFN-α2a ) , and intravenous 5-fluorouracil ( iv-5-FU ) according to the st and ard Atzpodien regimen ( Atzpodien et al , 2004 ) or ( B ) observation . Two- , 5- , and 8-year survival rates were 81 , 58 , and 58 % in the treatment arm , and 91 , 76 , and 66 % in the observation arm ( log rank P=0.0278 ) , with a median follow-up of 4.3 years . Two , 5- , and 8-year relapse-free survival rates were calculated at 54 , 42 , and 39 % in the treatment arm , and at 62 , 49 , and 49 % in the observation arm ( log rank P=0.2398 ) . Stage-adapted subanalyses revealed no survival advantages of treatment over observation , as well . Our results established that there was no relapse-free survival benefit and the overall survival was inferior with an adjuvant 8-week-outpatient sc-rIL-2/sc-rIFN-α2a/iv-5-FU-based immunochemotherapy compared to observation in high-risk renal cell carcinoma patients following radical tumour nephrectomy PURPOSE Because interferon gave promising results in the management of metastatic renal cell carcinoma in the 1980s , a multicentric r and omized controlled trial was planned to compare adjuvant recombinant interferon alfa-2b ( rIFNalpha2b ) with observation after radical nephrectomy in patients with Robson stages II and III renal cell carcinoma .  Overall and event-free survival were to be evaluated together with prognostic factors . PATIENTS AND METHODS  Overall and event-free survival curves for 247 patients ( 124 controls and 123 treated ) were estimated by the Kaplan-Meier method and compared using the log-rank test . Cox 's multiple regression models were adopted to perform a joint analysis of treatment and prognostic factors . RESULTS The 5-year overall and event-free survival probabilities were 0.665 and 0.671 , respectively , for controls and 0.660 and 0.567 , respectively , for the treated group ; the differences were not statistically significant ( 2P = .861 for overall and 2P = .107 for event-free survival with the log-rank test ) . Regarding prognostic factors , only grade , pT , and pN demonstrated a significant prognostic role . First-order interactions of treatment with pT and pN category were investigated ; a significant interaction was found between pN and treatment . A harmful effect of rIFNalpha2b in the 97 treated pN0 patients and a protective effect in the 13 treated pN2/pN3 patients were statistically significant . CONCLUSION Adjuvant rIFNalpha2b is not indicated after radical nephrectomy for renal cell carcinoma . The protective effect in the small group of pN2/pN3 patients requires further investigation Active specific immunotherapy ( ASI ) is a strategy that attempts to boost the host 's immune response specifically against its own tumor . The purpose of this study was to investigate the effect of adjuvant ASI in patients with renal carcinoma PURPOSE This prospect i ve , r and omized , controlled phase III trial assessed high-dose bolus interleukin-2 ( IL-2 ) postoperatively in patients with high-risk renal cell carcinoma ( RCC ) . PATIENTS AND METHODS Eligibility requirements were resected locally advanced ( LA ; T3b-4 or N1 - 3 ) or metastatic ( M1 ) RCC , no prior systemic therapy , and excellent organ function . R and omized assignment was to one course of IL-2 ( 600,000 U/kg every 8 hours on days 1 to 5 and days 15 to 19 [ maximum 28 doses ] ) or observation . The study was design ed and powered to show an improvement in predicted 2-year disease-free survival ( DFS ) from 40 % for the observation group to 70 % for the treatment group . The accrual goal was 68 patients with LA disease , with 34 patients per treatment arm . Metastasectomy patients were to be analyzed separately because of their unpredictable natural history . RESULTS Sixty-nine patients were enrolled onto the study ( 44 LA and 25 M1 patients ) .  Toxic effects of IL-2 were as anticipated ; no unexpected serious adverse events or treatment-related deaths occurred . Early closure occurred when an interim analysis determined that the 30 % improvement in 2-year DFS could not be achieved despite full accrual . Sixteen of 21 LA patients receiving IL-2 experienced relapse , compared with 15 of 23 patients in the observation arm ( P = .73 ) ; in the LA group , three deaths occurred in the IL-2 arm , and five deaths occurred in the observation arm ( P = .38 ) . Analysis including metastasectomy patients made no difference in DFS or overall survival . CONCLUSION One course of high-dose bolus IL-2 , though feasible , did not produce the ambitious clinical ly meaningful benefit anticipated when administered postoperatively to patients with resected high-risk RCC PURPOSE To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma . PATIENTS AND METHODS A total of 283 eligible patients with pT3 - 4a and /or node-positive disease were r and omly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL ( Wellferon , Burroughs-Wellcome , Research Park , NC ) given daily for 5 days every 3 weeks for up to 12 cycles . Patients were stratified on the basis of pathologic stage . Patients remained on treatment until documented recurrence , excessive toxicity , or patient/physician preference deemed removal appropriate . RESULTS At median follow-up of 10.4 years , median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm ( log-rank P = .09 ) . Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm ( P = .33 ) . Performance status ( P = .003 ) , nodal status ( N2 v N0 , P < .0001 ) , and tumor stage ( P = .0002 ) were significant prognostic factors in multivariate analysis . A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that r and om assignment to interferon treatment ( P = .009 ) and shorter time to recurrence ( P < .0001 ) were independent predictors of shorter survival after recurrence . Although no lethal toxicities were observed , severe ( grade 4 ) toxicities including neutropenia , myalgia , fatigue , depression , and other neurologic toxicities occurred in 11.4 % of those r and omly assigned to interferon treatment . CONCLUSION Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients PURPOSE To up date response duration and survival data for patients with metastatic renal cell carcinoma treated with high-dose interleukin (IL)-2 .  PATIENTS AND METHODS Two hundred fifty-five assessable patients were entered onto seven phase II clinical trials . Recombinant IL-2 600,000 or 720,000 IU/kg was administered by 15-minute intravenous infusion every 8 hours for up to 14 consecutive doses over 5 days as clinical ly tolerated with maximal support . A second , identical cycle of treatment was scheduled following 5 to 9 days of rest , and courses could be repeated every 6 to 12 weeks in stable or responding patients . All data were up date d as of December 1998 , with report forms completed by the clinical investigators . These data had last been up date d as part of the Food and Drug Administration reporting requirements in 1996 . RESULTS Objective responses previously have been reported in 37 of 255 patients ( 15 % ) with 17 complete responses ( 7 % ) and 20 partial responses ( 8 % ) . These data remain unchanged from previous reports . Median response duration for all objective responders remains unchanged at 54 months , but the range now extends from 3 to > 131 months . Median duration for all complete responses has not yet been reached , but was at least 80 months ( range , 7- > 131 mo ) at the time of this analysis . Median duration for all partial responses remains 20 months ( range , 3- > 126 mo ) . Median survival time for all 255 patients remains 16.3 months , with 10 % to 20 % of patients estimated to be alive 5 to 10 years after treatment with high-dose IL-2 . CONCLUSION With prolonged follow-up , treatment with high-dose recom 
    Output:
    