Epileptogenesis and oncogenesis: An antineoplastic role for antiepileptic drugs in brain tumours?

Cucchiara, Federico; Pasqualetti, Francesco; Giorgi, Filippo Sean; Danesi, Romano; Bocci, Guido

doi:10.1016/j.phrs.2020.104786

Cited by 24 publications

(24 citation statements)

References 227 publications

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“…A direct antitumor effect or an enhancement of antineoplastic drugs action has been advocated for some AEDs (i.e., valproic acrid, levetiracetam, perampanel, brivaracetam, and lacosamide) and some common pathways between epileptogenicity and glioma oncogenesis have been identified [ 150 , 157 , 158 ], but prospective clinical studies focusing on anticancer activity of AEDs are still lacking.…”

Section: Epilepsy In Low-grade Gliomamentioning

confidence: 99%

Clinical Management of Diffuse Low-Grade Gliomas

Lombardi

Barresi

Castellano

et al. 2020

Cancers

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Diffuse low-grade gliomas (LGG) represent a heterogeneous group of primary brain tumors arising from supporting glial cells and usually affecting young adults. Advances in the knowledge of molecular profile of these tumors, including mutations in the isocitrate dehydrogenase genes, or 1p/19q codeletion, and in neuroradiological techniques have contributed to the diagnosis, prognostic stratification, and follow-up of these tumors. Optimal post-operative management of LGG is still controversial, though radiation therapy and chemotherapy remain the optimal treatments after surgical resection in selected patients. In this review, we report the most important and recent research on clinical and molecular features, new neuroradiological techniques, the different therapeutic modalities, and new opportunities for personalized targeted therapy and supportive care.

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Section: Epilepsy In Low-grade Gliomamentioning

confidence: 99%

Clinical Management of Diffuse Low-Grade Gliomas

Lombardi

Barresi

Castellano

et al. 2020

Cancers

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“…β-oxidation [27]. Some recent evidence suggests that VPA might also mildly induce UGT1A1 when prescribed at high doses [28]. Surprisingly, not many studies analyzed VPA plasma monitoring.…”

Section: Description Of the Lithium And Vpa Blood Samples During The ...mentioning

confidence: 99%

“…The major routes of VPA metabolism are the glucuronidation and β-oxidation [27]. Some recent evidence suggests that VPA might also mildly induce UGT1A1 when prescribed at high doses [28].…”

Section: Introductionmentioning

confidence: 99%

A 5-Year Study of Lithium and Valproic Acid Drug Monitoring in Patients with Bipolar Disorders in an Italian Clinical Center

et al. 2022

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Therapeutic drug monitoring (TDM) is an effective tool used to improve the pharmacological treatment in clinical practice, especially to detect subtherapeutic drug plasma concentration (Cp) in order to consider a change of dosage during treatment and reach its putative therapeutic range. In this study, we report the Cp values of lithium and valproic acid (VPA), alone and in combination, mostly in bipolar patients admitted to an Italian clinical center of the University of Pisa during the years 2016–2020, which include 12,294 samples of VPA, 7449 of lithium and 1118 of both in combination. Lithium and VPA are the most utilized drugs in treating bipolar disorders, and their TDM is strongly recommended by recent guidelines. In relation to lithium Cp monitoring, several studies have underlined that 0.5–0.8 mmol/L is the optimal range for chronic treatment, and below 0.4 mmol/L, it is unlikely to produce a clinical response. For VPA, the therapeutic range is 50–100 μg/mL and a linear correlation between Cp and clinical efficacy has been proposed, where below 50 μg/mL, the clinical efficacy of VPA has not been proven thus far. Toxic levels of both drugs were rarely found in our study, while a high percentage of patients, about one-third, had sub-therapeutic Cp during their treatments. In addition, in several cases of patients receiving multiple blood sampling, the initial subtherapeutic Cp changed only partially without reaching its therapeutic window. In relation to age, we found a higher percentage of lithium and VPA Cp values in range in the adolescents than in the adults and elderly groups. No differences were reported when analyzing the distribution of Cp values in males and females. In conclusion, this present study suggests that TDM is widely used by many specialists, but there is still a window of improvement for optimizing pharmacological treatments in clinical practice.

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“…Mechanisms of BTRE have been partly explained and probably depend on intrinsic epileptogenicity (e.g., changes in neuro-transmitter balancing) and modification of the peritumoral environment (e.g., alteration of blood-brain barrier (BBB) and glial gap-junctional transmembrane communication proteins) especially in low grade tumors (9). High grade gliomas (HGG) determine epileptic seizures most probably through necrosis, hemosiderin deposition, hypoxia, and edema.…”

Section: Mechanisms and Risk Factorsmentioning

confidence: 99%

“…Conversely, an antineoplastic role has been postulated for AEDs, which can directly contribute to improve overall survival (9). Several studies have shown that valproate, used during RT and the temozolomide course, improves overall survival (35-39).…”

Section: Management Of Btrementioning

confidence: 99%

Seizures, Edema, Thrombosis, and Hemorrhages: An Update Review on the Medical Management of Gliomas

et al. 2021

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Patients affected with gliomas develop a complex set of clinical manifestations that deeply impact on quality of life and overall survival. Brain tumor-related epilepsy is frequently the first manifestation of gliomas or may occur during the course of disease; the underlying mechanisms have not been fully explained and depend on both patient and tumor factors. Novel treatment options derive from the growing use of third-generation antiepileptic drugs. Vasogenic edema and elevated intracranial pressure cause a considerable burden of symptoms, especially in high-grade glioma, requiring an adequate use of corticosteroids. Patients with gliomas present with an elevated risk of tumor-associated venous thromboembolism whose prophylaxis and treatment are challenging, considering also the availability of new oral anticoagulant drugs. Moreover, intracerebral hemorrhages can complicate the course of the illness both due to tumor-specific characteristics, patient comorbidities, and side effects of antithrombotic and antitumoral therapies. This paper aims to review recent advances in these clinical issues, discussing the medical management of gliomas through an updated literature review.

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Epileptogenesis and oncogenesis: An antineoplastic role for antiepileptic drugs in brain tumours?

Cited by 24 publications

References 227 publications

Clinical Management of Diffuse Low-Grade Gliomas

Clinical Management of Diffuse Low-Grade Gliomas

A 5-Year Study of Lithium and Valproic Acid Drug Monitoring in Patients with Bipolar Disorders in an Italian Clinical Center

Seizures, Edema, Thrombosis, and Hemorrhages: An Update Review on the Medical Management of Gliomas

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