A phase 2 clinical trial of sequential neoadjuvant chemotherapy with ifosfamide, doxorubicin, and gemcitabine followed by cisplatin, gemcitabine, and ifosfamide in locally advanced urothelial cancer Outcomes after adjuvant chemotherapy in the treatment of high‐risk urothelial carcinoma of the upper urinary tract (UUT‐UC) The result of adjuvant chemotherapy for localized pT3 upper urinary tract carcinoma in a multi-institutional study Adjuvant chemotherapy with paclitaxel and carboplatin in patients with advanced carcinoma of the upper urinary tract: a study by the Hellenic Cooperative Oncology Group. Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, fluorouracil, and leucovorin in stage III colon cancer: Cancer and Leukemia Group B Protocol 89803. Adjuvant methotrexate, vinblastine, adriamycin, and cisplatin chemotherapy has potential to prevent recurrence of bladder tumors after surgical removal of upper urinary tract transitional cell carcinoma.
Neoadjuvant chemotherapy improves the survival of patients with high‐risk urothelial cancer . However , the lack of curative alternatives to cisplatin‐based chemotherapy is limiting for patients with neuropathy or hearing loss  .  Sequential chemotherapy also has not been well studied in the neoadjuvant setting . The authors explored sequential neoadjuvant ifosfamide‐based chemotherapy in a patient cohort at high risk of noncurative cystectomy Urothelial carcinoma of the upper urinary tract ( UUT‐UC ) was a rare , aggressive urologic cancer with a propensity for multifocality , local recurrence , and metastasis . High‐risk patients had poor outcomes . Because of the rarity of these tumors , r and omized clinical trials and data regarding adjuvant chemotherapy in locally advanced tumors are currently unavailable . Our objective was to assess the effect of adjuvant chemotherapy and the impact of potential prognostic factors on survival in high‐risk , postsurgical UUT‐UC patients Purpose To determine through the analysis of our multi-institutional data base whether postoperative adjuvant chemotherapy for upper urinary tract carcinoma with localized invasive upper urinary tract carcinoma ( UUTC ) is beneficial . Methods A study population of 93 patients with pT3N0/xM0 UUTC was eligible for this study . Clinical features evaluated were sex , tumor location ,  adjuvant chemotherapy status , tumor pathology ( histology , grade , infiltrating growth , lymphovascular invasion ( LVI ) ) , and cause of death . Cancer-specific survival ( CSS ) was estimated by Kaplan – Meier method . Prognostic factors related to CSS were analyzed by Cox proportional hazards regression model for multivariate analysis . Results In pT3 patients , overall 5-year CSS rate was 68.4 % and median CSS time was 31 months ( range 3–114 months ) . In the adjuvant chemotherapy group , 5-year CSS rate was 80.8 % , whereas 5-year CSS rate was 64.4 % in the non-adjuvant chemotherapy group . By multivariate analysis , adjuvant chemotherapy status was significantly associated with CSS ( P = 0.008 ) were sex , tumor grade , tumor histology , and LVI presence . Conclusions This study , although it was retrospective study , revealed that adjuvant chemotherapy after RNU may be beneficial in pT3N0/X patients by multivariate analysis . Prospect i ve studies evaluating adjuvant therapy regimens for UTTC are required PURPOSE Radical surgery represents the treatment of choice for carcinoma of the upper urinary tract . Nevertheless , approximately 50 % of patients with stage T > /= 3 or lymph node involvement die from their disease , mainly as a result of the development of distant metastases . Therefore , there is a need for effective adjuvant systemic treatment . We prospect ively studied a cohort of patients who underwent surgery for high-risk carcinoma of the upper urinary tract to assess the feasibility of the combination of paclitaxel and carboplatin as adjuvant treatment . PATIENTS AND METHODS Thirty-six patients with tumor stage > /= 3 or lymph node involvement were treated with four cycles of paclitaxel at 175 mg/m(2 ) and carboplatin ( area under the curve 5 , Calvert Formula ) every 3 weeks following surgery . RESULTS Median follow-up was 40.6 months . Chemotherapy was well tolerated with 32 patients ( 89 % ) receiving full carboplatin and paclitaxel doses without delays . The most frequent grade 3/4 toxicity was neutropenia ( 39 % ) , which was complicated with fever in only one case ( 3 % ) . Nonhematologic grade 3 or 4 toxicities were reported in only one case . Five-year survival was 52 % ( 95 % CI , 35 % to 69 % ) , while 5-year disease-free survival was 40.2 % ( 95 % CI , 15.8 % to 64.6 % ) . Local failure rate was 30 % , as opposed to 17 % of patients who developed distant metastases . No patients with grade 2 tumors relapsed during follow-up , as opposed to 60 % of patients with grade 3 tumors . CONCLUSION Adjuvant chemotherapy with paclitaxel and carboplatin is feasible and may reduce the risk of distant metastases in high-risk upper urinary tract carcinoma PURPOSE Colon cancers exhibiting DNA mismatch repair ( MMR ) defects demonstrate distinct clinical and pathologic features , including better prognosis and reduced response to fluorouracil ( FU ) -based chemotherapy . This prospect i ve study investigated adjuvant chemotherapy containing FU and irinotecan in patients with MMR deficient ( MMR-D ) colon cancers . PATIENTS AND METHODS Cancer and Leukemia Group B 89803 r and omly assigned 1,264 patients with stage III colon cancer to postoperative weekly bolus FU/leucovorin ( LV ) or weekly bolus irinotecan , FU , and LV ( IFL ) .  The primary end point was overall survival ; disease-free survival ( DFS ) was a secondary end point . Tumor expression of the MMR proteins , MLH1 and MSH2 , was determined by immunohistochemistry ( IHC ) . DNA microsatellite instability was also assessed using a panel of mono- and dinucleotide markers . Tumors with MMR defects were those demonstrating loss of MMR protein expression ( MMR-D ) and /or microsatellite instability high ( MSI-H ) genotype . RESULTS Of 723 tumor cases examined by genotyping and IHC , 96 ( 13.3 % ) were MMR-D/MSI-H. Genotyping results were consistent with IHC in 702 cases ( 97.1 % ) . IFL-treated patients with MMR-D/MSI-H tumors showed improved 5-year DFS as compared with those with mismatch repair intact tumors ( 0.76 ; 95 % CI , 0.64 to 0.88 v 0.59 ; 95 % CI , 0.53 to 0.64 ; P = .03 ) . This relationship was not observed among patients treated with FU/LV . A trend toward longer DFS was observed in IFL-treated patients with MMR-D/MSI-H tumors as compared with those receiving FU/LV ( 0.57 ; 95 % CI , 0.42 to 0.71 v 0.76 ; 95 % CI , 0.64 to 0.88 ; P = .07 ; hazard ratio interaction between tumor status and treatment , 0.51 ; likelihood ratio P = .117 ) . CONCLUSION Loss of tumor MMR function may predict improved outcome in patients treated with the IFL regimen  as compared with those receiving FU/LV OBJECTIVES To evaluate the efficacy of adjuvant platinum based chemotherapy in upper urinary tract urothelial cancer following surgical resection in terms of survival benefit and inhibition of bladder cancer recurrence . METHODS Between April 1986 and August 2005 , a total of 132 patients with a diagnosis of upper urinary tract urothelial cancer underwent radical nephroureterectomy with cuff of bladder at our department . A total of 46 patients ( 13 with pT2pN0M0 and 33 with pT3 pN0M0 transitional cell carcinoma without prior bladder cancer ) were enrolled . Patients with locally advanced disease were divided into two groups : the adjuvant chemotherapy group ( 24 patients ) who received adjuvant methotrexate , vinblastine , adriamycin , and cisplatin ( M-VAC ) and the non-adjuvant chemotherapy group who did not receive adjuvant M-VAC ( 22 patients ) . RESULTS There were no statistically significant differences in patient characteristics or 10-year survival between the two groups . The recurrence rate in the non-adjuvant chemotherapy group was significantly higher than in the adjuvant chemotherapy group ( log-rank test , P < 0.0001 ) . Only non-adjuvant chemotherapy was a significant and independent risk factor ( hazard ratio 6.97 ) for the development of intravesical recurrence ( P < 0.01 ) . CONCLUSION Adjuvant M-VAC is an important optional adjuvant therapy and can prevent recurrent bladder tumors following surgery for upper urinary tract transitional cell carcinoma . To determine whether adjuvant chemotherapy has further benefit , a r and omized study would be needed
CONTEXT The role of adjuvant chemotherapy ( AC ) or neoadjuvant chemotherapy ( NC ) remains poorly defined for the management of upper tract urothelial carcinoma ( UTUC ) , although some studies suggest a benefit .
OBJECTIVE To up date the current evidence on the role of NC and AC for UTUC patients .