Randomized trial of adjuvant thalidomide versus observation in patients with completely resected high-risk renal cell carcinoma. Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: Results of a prospectively randomised Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN) Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study. Adjuvant immunotherapy treatment of renal carcinoma patients with autologous tumor cells and Bacillus Calmette‐Guèrin: Five‐year results of a prospective randomized study Adjuvant high-dose bolus interleukin-2 for patients with high-risk renal cell carcinoma: a cytokine working group randomized trial. Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial. Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Interferon alfa-2a in advanced renal cell carcinoma: treatment results and survival in 159 patients with long-term follow-up. An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial Postoperative UFT adjuvant and the risk factors for recurrence in renal cell carcinoma: a long-term follow-up study. Kyushu University Urological Oncology Group. Adjuvant medroxyprogesterone acetate to radical nephrectomy in renal cancer: 5-year results of a prospective randomized study.
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 recombinant IL-2 remains extremely effective for a subset of patients with metastatic renal cell carcinoma PURPOSE Three trials were conducted to define the efficacy and toxicity of interferon alfa-2a in the treatment of metastatic renal cell cancer . Univariate and multivariate analyses were performed to identify prognostic factors for survival . PATIENTS AND METHODS Prospect ively , 159 patients were treated with interferon alfa-2a .  In the first trial , 42 patients received 50 x 10(6 ) U/m2 intramuscularly three times per week . In the second trial , 64 patients received gradually escalating doses of interferon alfa-2a from 3 to 36 x 10(6 ) U subcutaneously administered daily . The third trial was r and omized ; 25 patients received daily interferon alfa-2a alone and 28 were treated with daily interferon alfa-2a and 0.15 mg/kg vinblastine every 3 weeks . RESULTS The overall response proportion was 10 % ( two complete and 14 partial responses ) . The median response duration was 12.2 months . The median survival duration was 11.4 months , with 3 % of patients alive at 5 or more years . A univariate statistical analysis showed that a Karnofsky performance status > or = 80 , prior nephrectomy , and interval from diagnosis to treatment of longer than 365 days were significant prognostic factors for survival . In a multivariate analysis , only prior nephrectomy and Karnofsky performance status > or = 80 were shown to be independent predictors of survival . CONCLUSION Interferon alfa-2a had minimal antitumor activity in patients with advanced renal cell carcinoma and long-term survival was achieved in a small proportion of patients . The need for continued investigation and the identification of more effective therapy for advanced renal cell carcinoma is evident from the poor overall survival rate observed in these 159 patients . The investigation of new agents and of interferon alfa-2a in combination with other agents remains a priority BACKGROUND Treatment of localised renal cell carcinoma consists of partial or radical nephrectomy . A substantial proportion of patients are at risk for recurrence because no effective adjuvant therapy exists . We investigated the use of an autologous , tumour-derived heat-shock protein ( glycoprotein 96)-peptide complex ( HSPPC-96 ; vitespen ) as adjuvant treatment in patients at high risk of recurrence after resection of locally advanced renal cell carcinoma . METHODS In this open-label trial , patients were r and omly assigned to receive either vitespen ( n=409 ) or observation alone ( n=409 ) after nephrectomy .  R and omisation was done in a one to one ratio by a computer-generated pseudo-r and om number generator , with a block size of four , and was stratified by performance score , lymph node status , and nuclear grade . Vitespen was given intradermally once a week for 4 weeks , then every 2 weeks until vaccine depletion . The primary endpoint was recurrence-free survival . The final analysis of recurrence-free survival was planned to take place after 214 or more events of disease recurrence or deaths before recurrence had occurred . Analysis was by intention to treat ( ITT ) . This study is registered with Clinical Trials.gov , number NCT00033904 . FINDINGS 48 patients in the vitespen group and 42 in the observation group were excluded from the ITT population because they did not meet post-surgery inclusion criteria ; the ITT population thus consisted of 361 patients in the vitespen group and 367 in the observation group . Final analysis of recurrence-free survival was triggered in November , 2005 . Re- review of all patients in the ITT population by the clinical events committee identified 149 actual recurrences ( 73 in the vitespen group and 76 in the observation group ) , nine deaths before recurrence ( two in the vitespen group and seven in the observation group ) , and 124 patients with baseline metastatic or residual disease ( 61 in the vitespen group and 63 in the observation group ) . Thus , after a median follow-up of 1.9 years ( IQR 0.9 - 2.5 ) in the ITT population , recurrence events were reported in 136 ( 37.7 % ) patients in the vitespen group and 146 ( 39.8 % ) in the observation group ( hazard ratio 0.923 , 95 % CI 0.729 - 1.169 ; p=0.506 ) . After continued follow-up until March , 2007 , there had been 70 deaths in the vitespen group and 72 in the observation group ( p=0.896 ) ; however , overall survival data were not mature , and patients continue to be followed up for survival . In predefined exploratory analyses by AJCC stage , recurrence events in patients with stage I or II disease were reported in 19 ( 15.2 % ) patients in the vitespen group and 31 ( 27.0 % ) in the observation group ( hazard ratio 0.576 , 95 % CI 0.324 - 1.023 ; p=0.056 ) . The most commonly reported adverse events in the vitespen group were injection-site erythema ( n=158 ) and injection-site in duration ( n=153 ) . One serious adverse event-autoimmune thyroiditis of grade 2 severity-was reported in the vitespen group ; no treatment-related grade 3 or 4 adverse events were reported . INTERPRETATION No difference in recurrence-free survival was seen between patients given vitespen and those who received no treatment after nephrectomy for renal cell carcinoma . A possible improvement in recurrence-free survival in patients with early stage disease who received vitespen  will require further validation BACKGROUND Radical nephrectomy is the st and ard therapy for low-stage renal cell carcinoma . However , recurrence sometimes develops even in patients who are considered to have undergone a curative resection of the primary tumor . The purpose of this study was to evaluate the usefulness of UFT ( a 1:4 mixture of tegafur and uracil ) adjuvant and the risk factors for recurrence in renal cell carcinoma . METHODS A prospect i ve r and omized trial was conducted to compare the use of long-term oral UFT adjuvant with nonadjuvant therapy after a radical nephrectomy for Robson stage I or II renal cell carcinoma . A multivariate analysis was also performed to estimate the risk factors for recurrence . RESULTS A total of 71 patients were entered into this study , and 66 were evaluable ( 33 for each group ) . There was no significant difference in patient characteristics between the 2 groups . The nonrecurrence rate at 5 years after a radical nephrectomy was 80.5 % and 77.1 % in the UFT adjuvant group and the nonadjuvant group , respectively , with a median follow-up of 112.9 months ; the difference was not significant . The toxicity of UFT was generally mild and tolerable . The tumor grade was found to be an important factor influencing recurrence . CONCLUSION UFT can not be universally recommended as an adjuvant therapy for radical nephrectomy in all patients with low-stage renal cell carcinoma From July 1 , 1979 to June 30 , 1983 , 136 consecutive patients from 5 centers in Lombardy entered a prospect i ve r and omized study to compare 500 mg . adjuvant medroxyprogesterone acetate 3 times a week for 1 year to no treatment  following radical nephrectomy for category M0 renal cancer . After a median followup of 5 years ( range 42 to 90 months ) 40 of 120 evaluable patients ( 33.3 per cent ) experienced relapse after a median interval free of disease of 17 months ( range 2 to 74 months ) . Relapses occurred in 19 of 58 evaluable patients in the adjuvant treatment group ( 32.7 per cent ) and in 21 of the 62 evaluable controls ( 33.9 per cent ) . Sex steroid hormone receptors were studied in 102 of the 120 evaluable patients with the dextran-coated charcoal technique . No significant correlation could be found among receptors , relapses and treatment . On the other h and , 33 ( 56.9 per cent ) of the 58 treated patients experienced 39 complications related to the long-term hormonal therapy . Three patients had to discontinue medroxyprogesterone acetate for severe toxicity after 2 to 3 months . Medroxyprogesterone acetate can not be recommended as adjuvant therapy to radical nephrectomy in patients with renal cell carcinoma
Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer .
However , no clear benefit has been identified to date .
This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting .