Current chemotherapy strategies in malignant pleural mesothelioma

Gooijer, Cornedine J. de; Baas, Paul; Burgers, Jacobus A.

doi:10.21037/tlcr.2018.04.10

Cited by 39 publications

(26 citation statements)

References 51 publications

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“…Chemotherapy regimens for patients with unresectable tumors usually consist of the combination of pemetrexed with a platinum agent (typically, cisplatin), either with or without bevacizumab. [4][5][6] However, even with multimodal therapy, treatment outcome for patients with MPM is poor, with most individuals dying within 2-3 years of diagnosis [7].…”

Section: Introductionmentioning

confidence: 99%

Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma

et al. 2019

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Objectives: CD26 is a transmembrane glycoprotein with dipeptidyl peptidase IV activity that is overexpressed in malignant pleural mesothelioma (MPM). We performed a phase I study to determine the maximum tolerated dose, pharmacokinetics, and antitumor activity of YS110, a monoclonal antibody to CD26, in Japanese patients with MPM intolerant of or refractory to prior standard therapies. Material and methods: The study was designed as an open-label, 3 + 3 dose-escalation, phase I trial. Patients were sequentially assigned to three dosing cohorts (2, 4, or 6 mg/kg). Each 6-week treatment cycle consisted of YS110 administration weekly for 5 weeks followed by a 1-week rest period. Treatment was continued until disease progression, death, or intolerable toxicity. Corticosteroid, antihistamine, and acetaminophen administration before each infusion was adopted to limit infusion-related reactions (IRRs). Results: Nine Japanese patients (seven men and two women, mean age of 62.2 years), three in each dosing cohort, were enrolled in the study. No patient developed a dose-limiting toxicity. Adverse events of grade 3 or 4 developed in seven patients, with the most common such event being a decreased lymphocyte count. Two patients had mild or moderate IRRs. The serum concentration of YS110 increased in a dose-dependent manner. Among seven patients evaluable for tumor response, four showed stable disease and one achieved a partial response. Conclusions: YS110 showed promising antitumor efficacy and was generally well tolerated in Japanese patients with advanced MPM at doses of up to 6 mg/kg. YS110 will be tested at 6 mg/kg in a subsequent phase II study.

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Section: Introductionmentioning

confidence: 99%

Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma

et al. 2019

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“…A phase 1 trial using miR-16 mimic incorporated with epidermal growth factor receptor (EGFR) targeting antibody called TargomiR, was used for patients with either recurrent malignant pleural mesothelioma or non-small cell lung cancer [ 159 , 160 ]. The findings were promising and showed that the miR-16 mimic is beneficial for patients with terminal mesothelioma patients with less than a 10% chance of 5-year survival [ 161 ]. A less successful 2013 phase 1 clinical trial investigated the miRNA-34 drug mimic MRX34 in patients with either primary liver cancer, solid tumours, or hematologic malignancy.…”

Section: Epigenetic Therapeutics In Cancer Clinical Trialsmentioning

confidence: 99%

Regulatory Mechanisms of Epigenetic miRNA Relationships in Human Cancer and Potential as Therapeutic Targets

Arif

Elliott

Haupt

et al. 2020

Cancers

104

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Initiation and progression of cancer are under both genetic and epigenetic regulation. Epigenetic modifications including alterations in DNA methylation, RNA and histone modifications can lead to microRNA (miRNA) gene dysregulation and malignant cellular transformation and are hereditary and reversible. miRNAs are small non-coding RNAs which regulate the expression of specific target genes through degradation or inhibition of translation of the target mRNA. miRNAs can target epigenetic modifier enzymes involved in epigenetic modulation, establishing a trilateral regulatory “epi–miR–epi” feedback circuit. The intricate association between miRNAs and the epigenetic architecture is an important feature through which to monitor gene expression profiles in cancer. This review summarises the involvement of epigenetically regulated miRNAs and miRNA-mediated epigenetic modulations in various cancers. In addition, the application of bioinformatics tools to study these networks and the use of therapeutic miRNAs for the treatment of cancer are also reviewed. A comprehensive interpretation of these mechanisms and the interwoven bond between miRNAs and epigenetics is crucial for understanding how the human epigenome is maintained, how aberrant miRNA expression can contribute to tumorigenesis and how knowledge of these factors can be translated into diagnostic and therapeutic tool development.

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“…It should be noted that these ndings impacted on long term overall outcome and no signi cant differences can be found by evaluating chemotherapy regimen and progression free survival in both men and female patients (Fig.1, panel III). Since no clear data are available in literature on the most bene cial conventional chemotherapy agent [ 20 , 21 ], we proceeded to analyze data regarding II line treatments. Speci cally, we compared the e cacy of gemcitabine (30 patients) vs vinorelbine (19 patients).…”

Section: Statistical Analysis and Data Miningmentioning

confidence: 99%

Integrating Data from Multidisciplinary Management of Malignant Pleural Mesothelioma: A Cohort Study

Saracino

Bortolotto

Tomaselli

et al. 2020

Preprint

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Background. Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy that most commonly affects the pleural lining of the lungs. MPM has a strong association with asbestos being at least 80% of cases caused by exposure to its biopersistent fibers. Individuals with a chronic exposure to asbestos might refer a 20-40-year latency with no or few symptoms. Such has been the case of Piedmont and Lombardy regions of Italy where industrial production of materials laden with asbestos, mainly cements, has created a large epidemic. Since 2018 in Pavia San Matteo hospital, a multidisciplinary team has been collecting data on over 100 patients with MPM. The main goal of this project is to define and describe an integrated profile for each MPM case at diagnosis by using data mining and partition analysis. Methods. Here we bring together exhaustive epidemiologic, histologic, radiologic data of 88 MPM patients that came to our observation to draw correlations with predictive and prognostic significance. Results. Overall, the median survival (OS) was of 15.6 months. Most patients presented with pleural effusion, irrespective of disease stage. Quite unexpectedly, no statistically significant association had been demonstrated between OS and TNM disease stage at diagnosis. Although average OS is similar in male and female patients, partition analysis of data underlined a significant differential hierarchy of predictor categories based on patient gender. In never smoker female patients, full chemotherapeutic regimens are associated to better outcomes. Moreover, within respect to second line treatments, vinorelbine emerged as the most advantageous choice but only in females, whereas in the male subgroup no statistically significant differences resulted between gemcitabine and vinorelbine. Conclusions. Multidisciplinary approach to MPM is thus mandatory to define better therapeutic approaches, personalize the management and improve patient outcomes.

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Current chemotherapy strategies in malignant pleural mesothelioma

Cited by 39 publications

References 51 publications

Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma

Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma

Regulatory Mechanisms of Epigenetic miRNA Relationships in Human Cancer and Potential as Therapeutic Targets

Integrating Data from Multidisciplinary Management of Malignant Pleural Mesothelioma: A Cohort Study

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