Somatic <i>ERCC2</i> Mutations Correlate with Cisplatin Sensitivity in Muscle-Invasive Urothelial Carcinoma

Allen, Eliezer M. Van; Mouw, Kent W.; Kim, Philip; Iyer, Gopa; Wagle, Nikhil; Al‐Ahmadie, Hikmat; Zhu, Cong; Ostrovnaya, Irina; Kryukov, Gregory V.; O’Connor, Kevin W.; Sfakianos, John P.; Garcia-Grossman, Ilana; Kim, Jaegil; Guancial, Elizabeth A.; Bambury, Richard; Bahl, Samira; Gupta, Namrata; Farlow, Deborah N.; Qu, Angela; Signoretti, Sabina; Barletta, Justine A.; Reuter, Victor E.; Boehm, Jesse S.; Lawrence, Michael S.; Getz, Gad; Kantoff, Philip W.; Bochner, Bernard H.; Choueiri, Toni K.; Bajorin, Dean F.; Solit, David B.; Gabriel, Stacey; D’Andrea, Alan D.; Garraway, Levi A.; Rosenberg, Jonathan E.

doi:10.1158/2159-8290.cd-14-0623

Cited by 544 publications

(396 citation statements)

References 38 publications

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“…Overall, these data point to pemetrexed, despite being well tolerated, as having at best modest efficacy in an unselected population of platinum-resistant advanced UC. Correlative tissue studies to identify molecular predictors of response to this and other agents may help improve their therapeutic index going forward [26]. We were unable to perform molecular tumor profiling of the responders in our cohort because archival tissue and/or patient consent were unavailable.…”

Section: Discussionmentioning

confidence: 99%

The Safety and Efficacy of Single-Agent Pemetrexed in Platinum-Resistant Advanced Urothelial Carcinoma: A Large Single-Institution Experience

et al. 2015

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Background. Pemetrexed is a commonly used treatment for platinum-resistant advanced urothelial carcinoma (UC) based on objective response rates of 8% and 28% in two small phase II studies. To address the discrepancy in reported response rates and to assess efficacy and toxicity outside of a clinical trial setting, we performed a large retrospective analysis of pemetrexed use at Memorial Sloan Kettering Cancer Center. We also investigated candidate prognostic factors for overall survival in this setting to explore whether the neutrophil-lymphocyte ratio (NLR) had independent prognostic significance. Patients and Methods. Patients receiving pemetrexed for platinum-resistant advanced UC between 2008 and 2013 were identified. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) were used to determine response rate. Kaplan-Meier and Cox regression analyses were used to examine the association of various factors with efficacy and survival outcomes. Hematologic toxicity and laboratory abnormalities were recorded.

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Section: Discussionmentioning

confidence: 99%

The Safety and Efficacy of Single-Agent Pemetrexed in Platinum-Resistant Advanced Urothelial Carcinoma: A Large Single-Institution Experience

et al. 2015

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“…The alterations may indicate possible therapeutic targets and lead to biomarker identification and predictive models, allowing assessment of chemoresponsiveness [19]. Our simple predictive model identifies patients with a high likelihood of achieving pR to help guide usage of GC NAC.…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes.

Gandhi¹,

Baras²,

Munari³

et al. 2015

JCO

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Purpose-To evaluate gemcitabine-cisplatin (GC) neoadjuvant cisplatin-based chemotherapy (NAC) for pathologic response (pR) and cancer-specific outcomes following radical cystectomy (RC) for muscle-invasive bladder cancer and identify clinical parameters associated with pR.Materials and methods-We studied 150 consecutive cases of muscle-invasive bladder cancer that received GC NAC followed by open RC (2000RC ( -2013. A cohort of 121 patients treated by RC alone was used for comparison. Pathologic response and cancer-specific survival (CSS) were compared. We created the Johns Hopkins Hospital Dose Index to characterize chemotherapeutic dosing regimens and accurately assess sufficient neoadjuvant dosing regarding patient tolerance.Results-No significant difference was noted in 5-year CSS between GC NAC (58%) and non-NAC cohorts (61%). The median follow-up was 19.6 months (GC NAC) and 106.5 months (non-NAC). Patients with residual non-muscle-invasive disease after GC NAC exhibit similar 5-year CSS relative to patients with no residual carcinoma (P = 0.99). NAC pR (≤pT1) demonstrated improved 5-year CSS rates (90.6% vs. 27.1%, P < 0.01) and decreased nodal positivity rates (0% vs. 41.3%, P < 0.01) when compared with nonresponders (≥pT2). Clinicopathologic outcomes were inferior in NAC pathologic nonresponders when compared with the entire RC-only-treated cohort. A lower pathologic nonresponder rate was seen in patients tolerating sufficient dosing of NAC as stratified by the Johns Hopkins Hospital Dose Index (P = 0.049), congruent with the National Comprehensive Cancer Network guidelines. A multivariate classification tree model demonstrated 60 years of age or younger and clinical stage cT2 as significant of NAC response (P < 0.05). *Corresponding author. Tel.: +1-314-488-5720. nilaymgandhi@gmail.com (N.M. Gandhi). 1 These authors contributed equally to this work and are to be considered co-first authors. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptConclusions-Pathologic nonresponders fare worse than patients proceeding directly to RC alone do. Multiple predictive models incorporating clinical, histopathologic, and molecular features are currently being developed to identify patients who are most likely to benefit from GC NAC.

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“…Using this technique, Di Stasi et al compared 6 weeks of induction therapy plus monthly BCG treatment for 9 months with sequential use of BCG and EMDA with MMC (EMDA-MMC) with an RCT including 212 patients. [53] In the latter protocol, patients received BCG for 2 weeks followed by 40 mg EMDA-MMC once a week as one cycle for 3 cycles. Furthermore, the latter group also received EMDA-MMC once a month for 2 months and followed by BCG once a month as one cycle for 3 months.…”

Section: Electromotive Drug Administrationmentioning

confidence: 99%

Alternative therapies in patients with non-muscle invasive bladder cancer

Şanlı

Lotan

2017

Turkish Journal of Urology

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Bladder cancer (BC) is one of the leading causes of cancer-related deaths worldwide. Despite, the majority of the cases were diagnosed as non-muscle invasive bladder cancer (NMIBC) with favorable prognosis, it has tendency to recur or progress to a higher grade or stage. The first line treatment of patients with NMIBC is transurethral resection with adjuvant therapies primarily intravesical Bacillus Calmette-Guérin (BCG) immunotherapy. However, in a portion of patients whose BCG treatment failed, alternative treatments may be required. Furthermore, intravesical BCG may be contraindicated in or untolerated by a group of patients. For these patients, some treatment options are readily available and a variety of them are currently under clinical investigation. In this review, these alternative therapies have been summarized.

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Somatic ERCC2 Mutations Correlate with Cisplatin Sensitivity in Muscle-Invasive Urothelial Carcinoma

Cited by 544 publications

References 38 publications

The Safety and Efficacy of Single-Agent Pemetrexed in Platinum-Resistant Advanced Urothelial Carcinoma: A Large Single-Institution Experience

The Safety and Efficacy of Single-Agent Pemetrexed in Platinum-Resistant Advanced Urothelial Carcinoma: A Large Single-Institution Experience

Gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma: Predicting response and assessing outcomes.

Alternative therapies in patients with non-muscle invasive bladder cancer

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