Sequential Intravesical Gemcitabine and Docetaxel for bacillus Calmette-Guérin-Naïve High-Risk Nonmuscle-Invasive Bladder Cancer

McElree, Ian M.; Steinberg, Ryan L.; Martin, Alex C.; Richards, Jordan; Mott, Sarah L.; Gellhaus, Paul T.; Nepple, Kenneth G.; O’Donnell, Michael A.; Packiam, Vignesh T.

doi:10.1097/ju.0000000000002740

Cited by 49 publications

(45 citation statements)

References 27 publications

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“…McElree et al (page 589) from Iowa City, Iowa retrospectively reviewed their center's experience of utilizing 6 weekly intravesical instillations of sequential gemcitabine and docetaxel for patients with BCG-na€ ıve high-risk nonmuscle-invasive bladder cancer. 3 They demonstrate impressive results for this doublet therapy in the BCG-na€ ıve setting with a 2-year risk of recurrence of 18% and no progression. Importantly, they also describe that the treatment in this disease space is well tolerated.…”

Section: Gemcitabine and Docetaxel For Nonmuscle-invasive Bladder Cancermentioning

confidence: 95%

This Month in Adult Urology

Siemens

2022

Journal of Urology

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Section: Gemcitabine and Docetaxel For Nonmuscle-invasive Bladder Cancermentioning

confidence: 95%

This Month in Adult Urology

Siemens

2022

Journal of Urology

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“…In a retrospective series by McElree et al, 107 patients with high-risk disease, including 44% with CIS, received gemcitabine for 90 min followed by docetaxel for 90–120 min as part of an induction once-a-week course for 6 weeks. Patients received once-a-month maintenance therapy if they were disease free at first surveillance [ 42 ]. The recurrence-free survival rate at 6 and 24 months was 89% and 82%, respectively, and was similar in patients with or without CIS.…”

Section: Intravesical Chemotherapymentioning

confidence: 99%

Novel Therapies for High-Risk Non-Muscle Invasive Bladder Cancer

Awamlh

Chang

2022

Curr Oncol Rep

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Purpose of Review The treatment options for high-risk non-muscle invasive bladder cancer (NMIBC), particularly following BCG, remain limited. We highlight recent, promising therapies for high-risk NMIBC. Recent Findings Several therapies utilizing different mechanisms of action have demonstrated favorable results in the BCG-naïve and BCG-unresponsive settings. These treatments include intravenous and intravesical immunotherapy, viral- and bacterial-based intravesical therapies, combination intravesical chemotherapy regimens, and novel intravesical chemotherapy administration. Overall, the efficacy and tolerability of emerging treatments for NMIBC appear promising and provide potential alternatives to radical cystectomy. Summary As the landscape of managing BCG-unresponsive disease evolves, clinical trials will explore future options and determine effective alternatives.

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“…However, few studies have combined low-dose decitabine with chemotherapy for the treatment of solid tumors. Here, we explore the efficacy and elucidate the mechanism of low-dose decitabine in combination with gemcitabine, a 4 chemotherapy commonly utilized in the treatment of many solid tumors including sarcoma, pancreatic, bladder, breast, ovarian, head and neck, and non-small cell lung cancers (16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Augmenting chemotherapy with low-dose decitabine through an immune-independent mechanism

Gutierrez¹,

Scherer²,

Rytlewski³

et al. 2022

JCI Insight

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The DNA methyltransferase inhibitor decitabine has classically been used to reactivate silenced genes and as a pre-treatment for anti-cancer therapies. In a new variation of this idea, this study explores the concept of adding low-dose decitabine following administration of chemotherapy to bolster therapeutic efficacy. We find that addition of decitabine following treatment with the chemotherapy agent gemcitabine improves survival and slows tumor growth in a mouse model of high-grade sarcoma. Unlike prior studies in epithelial tumor models, low-dose decitabine did not induce a robust anti-tumor T cell response in sarcoma. Furthermore, low-dose decitabine synergizes with gemcitabine independently of the immune system. Mechanistic analyses demonstrate that the combination therapy induces bi-phasic cell cycle arrest and apoptosis. Therapeutic efficacy was found to be sequence dependent, with gemcitabine priming cells for treatment with decitabine through inhibition of ribonucleotide reductase. This study identifies a unique application of low-dose decitabine to augment the cytotoxic effects of conventional chemotherapy in an immune-independent manner.The concepts explored in this study represent a promising new paradigm for cancer treatment by augmenting chemotherapy through addition of low-dose decitabine to increase tolerability and improve patient response. These findings have widespread implications for the treatment of sarcomas and other aggressive malignancies.

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Sequential Intravesical Gemcitabine and Docetaxel for bacillus Calmette-Guérin-Naïve High-Risk Nonmuscle-Invasive Bladder Cancer

Cited by 49 publications

References 27 publications

This Month in Adult Urology

This Month in Adult Urology

Novel Therapies for High-Risk Non-Muscle Invasive Bladder Cancer

Augmenting chemotherapy with low-dose decitabine through an immune-independent mechanism

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