BACKGROUND: Customizing chemotherapy on the basis of chemosentitivity prediction may improve outcome in advanced bladder cancer patients. Since DNA damaging agents are the cornerstones of therapy, we hypothesized that levels of DNA repair genes could predict survival. PATIENTS AND METHODS: Messenger RNA expression levels of excision repair cross complementing 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and caveolin-1 were determined by RT-PCR in tumor DNA from 57 advanced and metastatic bladder cancer patients treated with either gemcitabine/cisplatin or gemcitabine/cisplatin/paclitaxel (Taxol). Levels were correlated with survival, time to disease progression and chemotherapy response. RESULTS: Median survival was significantly higher in patients with low ERCC1 levels (25.4 versus 15.4 months; P = 0.03) (median follow-up 19 months). A trend towards longer time to progression was observed in patients with tumors expressing low levels of all markers. Levels of RRM1, BRCA1 and caveolin-1, however, failed to predict the survival and a clear link with chemotherapy response could not be established. On multivariate analysis with pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for survival. CONCLUSION: The results of the study indicate that ERCC1 may predict survival in bladder cancer treated by platinum-based therapy.
BACKGROUND: Customizing chemotherapy on the basis of chemosentitivity prediction may improve outcome in advanced bladder cancerpatients. Since DNA damaging agents are the cornerstones of therapy, we hypothesized that levels of DNA repair genes could predict survival. PATIENTS AND METHODS: Messenger RNA expression levels of excision repair cross complementing 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase subunit M1 (RRM1) and caveolin-1 were determined by RT-PCR in tumor DNA from 57 advanced and metastatic bladder cancerpatients treated with either gemcitabine/cisplatin or gemcitabine/cisplatin/paclitaxel (Taxol). Levels were correlated with survival, time to disease progression and chemotherapy response. RESULTS: Median survival was significantly higher in patients with low ERCC1 levels (25.4 versus 15.4 months; P = 0.03) (median follow-up 19 months). A trend towards longer time to progression was observed in patients with tumors expressing low levels of all markers. Levels of RRM1, BRCA1 and caveolin-1, however, failed to predict the survival and a clear link with chemotherapy response could not be established. On multivariate analysis with pretreatment prognostic factors, ERCC1 emerged as an independent predictive factor for survival. CONCLUSION: The results of the study indicate that ERCC1 may predict survival in bladder cancer treated by platinum-based therapy.
Authors: Lauren C Harshman; Gerold Bepler; Zhong Zheng; John P Higgins; Genevera I Allen; Sandy Srinivas Journal: BJU Int Date: 2010-12 Impact factor: 5.588
Authors: Joshua R Heyza; Wen Lei; Donovan Watza; Hao Zhang; Wei Chen; Jessica B Back; Ann G Schwartz; Gerold Bepler; Steve M Patrick Journal: Clin Cancer Res Date: 2018-12-11 Impact factor: 12.531
Authors: Aurélie Mbeutcha; Ilaria Lucca; Vitaly Margulis; Jose A Karam; Christopher G Wood; Michela de Martino; Romain Mathieu; Andrea Haitel; Evanguelos Xylinas; Luis Kluth; Morgan Rouprêt; Pierre I Karakiewicz; Alberto Briganti; Michael Rink; Malte Rieken; Alon Z Weizer; Jay D Raman; Nathalie Rioux-Leclecq; Christian Bolenz; Karim Bensalah; Yair Lotan; Christian Seitz; Mesut Remzi; Shahrokh F Shariat; Tobias Klatte Journal: World J Urol Date: 2015-12-11 Impact factor: 4.226