Bladder preservation by combined modality therapy for invasive bladder cancer.

Kachnic, Lisa A.; Kaufman, Donald S.; Heney, Niall M.; Althausen, Alex F.; Griffin, Pamela P.; Zietman, Anthony L.; Shipley, William U.

doi:10.1200/jco.1997.15.3.1022

Cited by 203 publications

(68 citation statements)

References 24 publications

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“…Several studies reported promising results using combined trimodality therapy in invasive bladder cancer with transurethral resection (TUR), radiation therapy and platinumbased systemic chemotherapy (1)(2)(3)(4). Those studies demonstrated 5-year survival rates of 50-65% and approximately three-quarters of the surviving patients maintained their own bladders.…”

Section: Introductionmentioning

confidence: 97%

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

Sakano

Ogawa

Yamamoto

et al. 2013

Molecular and Clinical Oncology

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Abstract. Combined trimodality therapy, including transurethral resection and platinum-based chemoradiotherapy, has shown promising results for muscle-invasive bladder cancer. However, this type of treatment may decrease survival as a result of delayed cystectomy in patients with non-responding tumors. DNA repair proteins may affect survival of bladder cancer patients receiving combined trimodality therapy, by affecting the perioperative nature of the tumor cells or by repairing DNA damaged by platinum agents and radiation. We investigated the associations of excision repair cross-complementing group 1 (ERCC1), X-ray repair cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with response and survival in 157 locally advanced bladder cancer patients receiving combined trimodality therapy, in order to determine the predictive value of the expression of these proteins in patient selection for therapy. We examined ERCC1, XRCC1 and APE1 expression in tumor specimens using immunohistochemistry. Patients positive for ERCC1, positive for XRCC1 and positive for either ERCC1 or XRCC1, exhibited significantly improved disease-specific survival rates (P=0.023, 0.025 and 0.0091, respectively). In multivariate analysis, combined ERCC1 and XRCC1 expression was independently associated with disease-specific mortality [risk ratio (RR): 0.64; 95% confidence interval (CI), 0.43-0.94 and P=0.024]. Thus, combined ERCC1 and XRCC1 expression may serve as an independent prognostic marker for survival in bladder cancer patients receiving combined trimodality therapy. Prospective studies with a larger sample size are required to confirm these results.

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Section: Introductionmentioning

confidence: 97%

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

Sakano

Ogawa

Yamamoto

et al. 2013

Molecular and Clinical Oncology

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“…With these programs, cystectomy is reserved for patients with an incomplete response or local relapse after combined-modality treatment. Five-year survival rates in the range of 50 -65% have been published in these series, and approximately three quarters of the surviving patients maintained their own bladders (Tester et al, 1996;Kachnic et al, 1997;Dunst et al, 2001). However, combined-modality therapy may not only be potentially harmful but also diminish survival as a result of the delay in cystectomy for some patients with nonresponding bladder tumours.…”

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confidence: 94%

Single nucleotide polymorphisms in DNA repair genes might be prognostic factors in muscle-invasive bladder cancer patients treated with chemoradiotherapy

et al. 2006

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DNA repair enzymes repair DNA damaged by platinum agents and ionising radiation. Single nucleotide polymorphisms (SNPs) in DNA repair genes modulate the repair capacity and might affect response and prognosis following platinum-based chemoradiotherapy (CRT). We investigated associations between the functional SNPs in DNA repair genes and response and survival in muscle-invasive bladder cancer patients treated with CRT to determine the predictive value of the SNPs in patient selection for bladder conservation therapy. The study group comprised 78 patients who underwent CRT for transitional cell carcinoma of the bladder. Single nucleotide polymorphisms in xeroderma pigmentosum complementation groups C (Lys939Gln, A/ C), D (XPD; Lys751Gln, A/C), and G (Asp1104His, G/C), and X-ray repair cross-complementing groups 1 (XRCC1; Arg399Gln, G/ A) and 3 (Thr241Met, T/C) genes were genotyped. Combined genotypes with at least one variant allele in XPD or XRCC1 were significantly associated with improved cancer-specific survival compared with remaining groups (P ¼ 0.009). In multivariate analysis, only the combined XPD and XRCC1 genotypes were independently associated with cancer-specific survival (P ¼ 0.04). The association was stronger in stage T3/T4 patients (P ¼ 0.0008). These results suggest that combined XPD and XRCC1 genotypes might be prognostic factors in muscle-invasive bladder cancer patients treated with CRT.

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“…The finding that the radiosensitizing effect of HER2 depletion plus erlotinib is not as good as the radiosensitizing effect of afatinib alone suggests that other factors may be involved, such as a higher affinity to EGFR (15) and inhibition of HER3 (36) or HER4 (37) by afatinib. In addition, because chemotherapeutic agents like cisplatin are widely used to enhance radiosensitivity in bladder cancer therapy (38,39), whether EGFR/ HER dual inhibition can further improve the outcome of chemoradiation deserves more studies. Finally, although we clearly demonstrated the in vivo benefit of afatinib to enhance radiosensitivity, the response of a subcutaneous tumor graft may differ from that of the orthotopic bladder tumor model (21).…”

Section: Discussionmentioning

confidence: 99%

Synergistic Blockade of EGFR and HER2 by New-Generation EGFR Tyrosine Kinase Inhibitor Enhances Radiation Effect in Bladder Cancer Cells

Tsai

Tzen

et al. 2015

Molecular Cancer Therapeutics

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Blockade of EGFR has been proved useful in enhancing the effect of radiotherapy, but the advantages of new-generation EGFR tyrosine kinase inhibitors (TKI) in radiosensitization are not well known. We used two human bladder cancer cells with wild-type EGFR to study the synergism between irradiation and afatinib (an EGFR/HER2 dual kinase inhibitor) or erlotinib (an EGFR kinase inhibitor). Here, we showed that afatinib has better radiosensitizing effect than erlotinib in increasing cancer cell killing, the percentage of apoptotic cells, and DNA damage. Afatinib is also superior to erlotinib in combining radiation to decrease tumor size, inhibit glucose metabolism, and enhance apoptotic proteins in vivo. Finally, erlotinib suppressed cell growth and induced more DNA damage in bladder cancer cells transfected with HER2 shRNA, but not in control vector-treated cells. In conclusion, concomitant blockade of radiation-activated EGFR and HER2 signaling by a new-generation EGFR TKI better inhibits the growth of bladder cancer cells both in vitro and in vivo. The absence of radiosensitization by EGFR inhibition alone and the greater radiosensitizing effect of EGFR inhibitor in HER2 knocked down cells suggest the synergism between HER2 and EGFR in determining radiosensitivity. The regained radiosensitizing activity of erlotinib implies that with proper HER2 inhibition, EGFR tyrosine kinase is still a potential target to enhance radiotherapy effect in these seemingly unresponsive bladder cancer cells.

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Bladder preservation by combined modality therapy for invasive bladder cancer.

Cited by 203 publications

References 24 publications

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

Single nucleotide polymorphisms in DNA repair genes might be prognostic factors in muscle-invasive bladder cancer patients treated with chemoradiotherapy

Synergistic Blockade of EGFR and HER2 by New-Generation EGFR Tyrosine Kinase Inhibitor Enhances Radiation Effect in Bladder Cancer Cells

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