Bendamustine: an Old Drug in the New Era for Patients with Non-Hodgkin Lymphomas and Chronic Lymphocytic Leukemia

Patekar, Martina Bogeljić; Milunović, Vibor; Jakobac, Karla Mišura; Perica, Dražen; Rogulj, Inga Mandac; Kursar, Marin; Planinc-Peraica, Ana; Kolonić, Slobodanka Ostojić

doi:10.20471/acc.2018.57.03.18

Cited by 13 publications

(11 citation statements)

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“…The MEK inhibitor selumetinib has shown anti-tumour effects in EC cell culture [ 201 ], whilst binimetinib is yet to be studied in EC. The chemotherapy agents chlorambucil, carmustine and bendamustine are frequently used in the treatment of haematological cancers, such as non-Hodgkin lymphoma and chronic lymphocytic leukaemia, but are yet to be studied in EC [ 202 , 203 , 204 , 205 ]. Our data also identified many novel drug agents that demonstrate anti-tumour activity in vitro and in vivo, and these include the anti-mesothelin immunotoxin SS1 (dsFv)-PE38, the PI3K inhibitor AZD-6482 and the cyclin-dependent kinase inhibitors variolin B, meriolin, alsterpaullone and dinaciclib [ 206 , 207 , 208 , 209 , 210 , 211 , 212 , 213 ].…”

Section: Discussionmentioning

confidence: 99%

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Bradfield

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Hill

et al. 2020

MPs

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Endometrial cancer (EC) is the commonest gynaecological malignancy. Current prognostic markers are inadequate to accurately predict patient survival, necessitating novel prognostic markers, to improve treatment strategies. Telomerase has a unique role within the endometrium, whilst aberrant telomerase activity is a hallmark of many cancers. The aim of the current in silico study is to investigate the role of telomere and telomerase associated genes and proteins (TTAGPs) in EC to identify potential prognostic markers and therapeutic targets. Analysis of RNA-seq data from The Cancer Genome Atlas identified differentially expressed genes (DEGs) in EC (568 TTAGPs out of 3467) and ascertained DEGs associated with histological subtypes, higher grade endometrioid tumours and late stage EC. Functional analysis demonstrated that DEGs were predominantly involved in cell cycle regulation, while the survival analysis identified 69 DEGs associated with prognosis. The protein-protein interaction network constructed facilitated the identification of hub genes, enriched transcription factor binding sites and drugs that may target the network. Thus, our in silico methods distinguished many critical genes associated with telomere maintenance that were previously unknown to contribute to EC carcinogenesis and prognosis, including NOP56, WFS1, ANAPC4 and TUBB4A. Probing the prognostic and therapeutic utility of these novel TTAGP markers will form an exciting basis for future research.

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Section: Discussionmentioning

confidence: 99%

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Bradfield

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Hill

et al. 2020

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“…13,14) Discontinuation or dose reduction of bendamustine alone or in BR therapy suggests that treatment intensity is reduced, which directly impacts survival. 16) Therefore, clarifying the risk factors for skin toxicities associated with bendamustine treatment may be useful for patient management.…”

Section: Introductionmentioning

confidence: 99%

Risk Factors for Skin Toxicities Associated with Bendamustine-Based Chemotherapy in Patients with Non-Hodgkin Lymphoma

Uchida

Mori

Akiba

et al. 2020

Biological & Pharmaceutical Bulletin

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Bendamustine plays an especially important role as a treatment for non-Hodgkin lymphoma (NHL). However, patients administered bendamustine alone or in combination with rituximab (BR) may experience drug-associated skin toxicities that can profoundly impact their health-related QOL through both physical discomfort and psychological distress. Moreover, worsening skin symptoms may lead to dose reduction or termination in the management of cancer chemotherapy. We retrospectively investigated patient backgrounds and pretreatment characteristics from medical records of NHL patients treated with bendamustine alone or BR therapy and identified predictive factors for skin toxicities at the start of chemotherapy. Patients were eligible for the study if they were 20 years older, diagnosed with NHL, and received bendamustine alone or BR therapy at the Department of Hematology, Kobe City Medical Center General Hospital, between April 1, 2011, and March 31, 2018. This study included 95 patients with newly diagnosed or refractory or relapsed NHL. Multivariate stepwise logistic regression analysis with backward selection revealed that baseline non-prior chemotherapy (odds ratio (OR), 15.72; 95% confidence interval (CI), 4.24-83.13, p < 0.001) was a significant factor influencing the occurrence of skin toxicity. Our results demonstrated that non-prior chemotherapy was a significant risk factor for skin toxicities in patients with NHL receiving bendamustine alone or BR therapy. No patient experience serious side effects of grade 3 or higher and that bendamustine is very useful as a first-line treatment.

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“…При сравнении эффективности бендамустина и флударабина бендамустин несколько превосходил флударабин как по частоте полных и частичных ответов, так и по медиане безрецидивной выживаемости, однако общая выживаемость также была одинаковой [33]. Несмотря на схожесть профилей токсичности, частота инфекционных и гематологических осложнений при применении бендамустина существенно ниже по сравнению с флударабином [34]. Эффективность бендамустина при лечении ХЛЛ подтверждена и другими многочисленными исследованиями.…”

Section: препараты применяемые для лечения хронического лимфоцитарного лейкозаunclassified

Modern Approaches to Treatment of Chronic Lymphocytic Leukemia

2020

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Purpose of the study: to systematize published data on the effectiveness of drugs used to treat patientswith chronic lymphocytic leukemia.Material and Methods. A literature search was conducted using Medline, Pubmed databases. 93 publications were selected to write this review.Results. General information about chronic lymphocytic leukemia (biological features, criteria for establishing diagnosis, staging, criteria for evaluating antitumor therapy response) was presented. The focus was made on antitumor drugs used as monotherapy and in combination with other anti-cancer agents. The use of drugs belonging to the classes of cytostatics, monoclonal antibodies, as well as drugs that affect the signaling pathways of the B-cell receptor, BCL -2 inhibitors, immunomodulators was discussed. The gold standard for first-line therapy remains the RFC scheme. With a positive Coombs test, bendamustine is an equivalent alternative to the FC regimen. The use of chlorambucil is limited in situations in which the goal of therapy is the palliative treatment of older people with serious comorbidity. In subsequent lines of therapy, molecular action drugs are beginning to take an increasingly important place.Conclusion. During the past twenty years, significant advances have been made in understanding biological features of chronic lymphocytic leukemia, the synthesis of several dozen new therapeutic drugs of targeted action, some of which are already undergoing clinical testing. These drugs may lead to serious complications. The review is devoted to new drugs, the efficacy and safety of which has already been tested in a clinical setting.

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Bendamustine: an Old Drug in the New Era for Patients with Non-Hodgkin Lymphomas and Chronic Lymphocytic Leukemia

Cited by 13 publications

References 60 publications

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Risk Factors for Skin Toxicities Associated with Bendamustine-Based Chemotherapy in Patients with Non-Hodgkin Lymphoma

Modern Approaches to Treatment of Chronic Lymphocytic Leukemia

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