Immunotherapy for the Treatment of Urothelial Carcinoma

Donin, Nicholas M.; Lenis, Andrew T.; Holden, Stuart; Drakaki, Alexandra; Pantuck, Allan J.; Belldegrun, Arie S.; Chamie, Karim

doi:10.1016/j.juro.2016.02.3005

Cited by 101 publications

(86 citation statements)

References 40 publications

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“…Immunotherapy represents a very promising area of multimodal treatment for many types of cancer (98)(99)(100)(101). There has also been great progress in immunotherapy research in GBM over the past few years.…”

Section: Immunotherapy Of Gbmmentioning

confidence: 99%

“…There has been dramatic success in the treatment of various advanced solid tumor types such as melanoma, renal cancer, lung cancer, head and neck cancer with the novel class of immunomodulatory anticancer agents called immune checkpoint inhibitors (98)(99)(100)(101)(119)(120)(121). These therapeutics are able to block inhibitory molecules and their receptors on effector immune cells, which leads to a robust T-cell response against the tumor.…”

Section: The Role Of Immune Checkpoint Inhibitors In Glioblastoma Immmentioning

confidence: 99%

“…Immune checkpoint inhibitors represent a significant breakthrough in the treatment of various advanced tumor types (such as melanoma, renal cancer, lung cancer, head and neck cancer, and urinary bladder cancer) in recent years that has dramatically changed the prognosis of patients with cancer (98)(99)(100)(101)(119)(120)(121). In some cases, therapy with these drugs means long-term disease control or hopefully even cure.…”

Section: The Role Of Immune Checkpoint Inhibitors In Glioblastoma Immmentioning

confidence: 99%

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Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

et al. 2017

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Abstract. Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single antiangiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed.Glioblastoma multiforme (GBM) belongs to the largest group of primary central nervous system (CNS) tumors, so-called gliomas, which are formed from supporting glial cells in the brain parenchyma (1, 2). GBM represents the most common and most malignant tumor in this class, with an incidence of 3-4/100,000/year (3, 4). GBM is an extremely invasive and difficult to treat tumor, characterized by intense and aberrant vascularization and high resistance to radiotherapy (RT) and chemotherapy (CHT). The current standard of care for patients with newly-diagnosed GBM comprises of neurosurgery and subsequent concomitant chemoradiotherapy by fractionated external-beam RT and systemic temozolomide followed by systemic temozolomide in the adjuvant setting (5). There are only very limited possibilities for the treatment of subsequent recurrences, generally with minimal clinical efficacy (6). Despite intensive multimodal treatment strategies, the median survival of patients with GBM is still 12.1-14.6 months and only 3-5% of patients survive longer than 3 years (7).Enormous progress has been made in the genetics and epigenetics of GBM during the past decade. The Cancer 21Τhis article is freely accessible online.Correspondence to: Jiri Polivka, Department of Neurology, Faculty Hospital Plzen, alej Svobody 80, 304 60, Plzen, Czech Republic. E-mail: polivka@fnplzen.cz Key Words: Glioblastoma multiforme, GBM, targeted therapy, immunotherapy, immune checkpoint inhibitors, PD1 inhibition, CTLA4 inhibition, clinical trials, personalized medicine, review. ANTICANCER RESEARCH 37: 21-34 (2017) [8][9][10][11][12]. The most important genetic...

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Section: Immunotherapy Of Gbmmentioning

confidence: 99%

Section: The Role Of Immune Checkpoint Inhibitors In Glioblastoma Immmentioning

confidence: 99%

Section: The Role Of Immune Checkpoint Inhibitors In Glioblastoma Immmentioning

confidence: 99%

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Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

et al. 2017

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“…However, it is known that BCG activates the immune system by adhering to urothelium and tumor cells through the action of fibronectin. [7] After being internalized, MHC class II molecules are upregulated and cytokine production is increased leading to immune mediated cytotoxicity. [7] A recent systematic review suggested that 6 weeks of induction therapy with BCG is associated with a decreased recurrence (RR 0.56 95% CI 0.43-0.1) and progression (RR 0.39, 95% CI 0.24-0.64) risk compared to TUR-BT alone.…”

Section: Introductionmentioning

confidence: 99%

“…[7] After being internalized, MHC class II molecules are upregulated and cytokine production is increased leading to immune mediated cytotoxicity. [7] A recent systematic review suggested that 6 weeks of induction therapy with BCG is associated with a decreased recurrence (RR 0.56 95% CI 0.43-0.1) and progression (RR 0.39, 95% CI 0.24-0.64) risk compared to TUR-BT alone. [8] Some patients may have contraindications to BCG and some patients and physicians may prefer to use intravesical chemotherapy in recurrent low grade tumors.…”

Section: Introductionmentioning

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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Bladder Cancer

Lenis

Lec

Chamie³

et al. 2020

JAMA

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1,145

812

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ImportanceBladder cancer is a common malignancy in women and is the fourth most common malignancy in men. Bladder cancer ranges from unaggressive and usually noninvasive tumors that recur and commit patients to long-term invasive surveillance, to aggressive and invasive tumors with high disease-specific mortality.ObservationsAdvanced age, male sex, and cigarette smoking contribute to the development of bladder cancer. Bladder tumors can present with gross or microscopic hematuria, which is evaluated with cystoscopy and upper tract imaging depending on the degree of hematuria and risk of malignancy. Non–muscle-invasive tumors are treated with endoscopic resection and adjuvant intravesical therapy, depending on the risk classification. Enhanced cystoscopy includes technology used to improve the detection of tumors and can reduce the risk of recurrence. Patients with high-risk non–muscle invasive tumors that do not respond to adjuvant therapy with the standard-of-care immunotherapy, bacille Calmette-Guérin (BCG), constitute a challenging patient population to manage and many alternative therapies are being studied. For patients with muscle-invasive disease, more aggressive therapy with radical cystectomy and urinary diversion or trimodal therapy with maximal endoscopic resection, radiosensitizing chemotherapy, and radiation is warranted to curb the risk of metastasis and disease-specific mortality. Treatment of patients with advanced disease is undergoing rapid changes as immunotherapy with checkpoint inhibitors, targeted therapies, and antibody-drug conjugates have become options for certain patients with various stages of disease.Conclusions and RelevanceImproved understanding of the molecular biology and genetics of bladder cancer has evolved the way localized and advanced disease is diagnosed and treated. While intravesical BCG has remained the mainstay of therapy for intermediate and high-risk non–muscle-invasive bladder cancer, the therapeutic options for muscle-invasive and advanced disease has expanded to include immunotherapy with checkpoint inhibition, targeted therapies, and antibody-drug conjugates.

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Immunotherapy for the Treatment of Urothelial Carcinoma

Cited by 101 publications

References 40 publications

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

Alternative therapies in patients with non-muscle invasive bladder cancer

Bladder Cancer

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