Antiepileptic drug use improves overall survival in breast cancer patients with brain metastases in the setting of whole brain radiotherapy

Reddy, Jay P.; Dawood, Shaheenah; Mitchell, Melissa; Debeb, Bisrat G.; Bloom, Elizabeth Stroh; González-Angulo, Ana M.; Sulman, Erik P.; Buchholz, Thomas A.; Woodward, Wendy A.

doi:10.1016/j.radonc.2015.10.009

Cited by 23 publications

(16 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VGSC inhibitors may also have an added benefit in combination with existing treatments. An observational study of records from 253 patients with BCa brain metastases who had undergone whole brain radiotherapy (WBRT) showed that the overall survival of those receiving antiepileptic drugs was significantly longer than for patients not receiving such medication, although this association may be due to reduced mortality from better control of seizures caused by WBRT [110]. Administration of anti-epileptic drugs improved overall survival in Her2 + BCa patients and those undergoing surgery [110].…”

Section: Clinical Studiesmentioning

confidence: 99%

“…An observational study of records from 253 patients with BCa brain metastases who had undergone whole brain radiotherapy (WBRT) showed that the overall survival of those receiving antiepileptic drugs was significantly longer than for patients not receiving such medication, although this association may be due to reduced mortality from better control of seizures caused by WBRT [110]. Administration of anti-epileptic drugs improved overall survival in Her2 + BCa patients and those undergoing surgery [110]. Suppressing the activation of VGSC-I NaP by certain chemotherapeutic drugs, including anthracyclines, could reduce the cardiotoxicity associated with standard-of-care therapies [111].…”

Section: Clinical Studiesmentioning

confidence: 99%

See 1 more Smart Citation

In Vivo Evidence for Voltage-Gated Sodium Channel Expression in Carcinomas and Potentiation of Metastasis

Djamgoz

Fraser

Brackenbury

2019

Cancers

View full text Add to dashboard Cite

A wide body of evidence suggests that voltage-gated sodium channels (VGSCs) are expressed de novo in several human carcinomas where channel activity promotes a variety of cellular behaviours integral to the metastatic cascade. These include directional motility (including galvanotaxis), pH balance, extracellular proteolysis, and invasion. Contrary to the substantial in vitro data, however, evidence for VGSC involvement in the cancer process in vivo is limited. Here, we critically assess, for the first time, the available in vivo evidence, hierarchically from mRNA level to emerging clinical aspects, including protein-level studies, electrolyte content, animal tests, and clinical imaging. The evidence strongly suggests that different VGSC subtypes (mainly Nav1.5 and Nav1.7) are expressed de novo in human carcinoma tissues and generally parallel the situation in vitro. Consistent with this, tissue electrolyte (sodium) levels, quantified by clinical imaging, are significantly higher in cancer vs. matched non-cancer tissues. These are early events in the acquisition of metastatic potential by the cancer cells. Taken together, the multi-faceted evidence suggests that the VGSC expression has clinical (diagnostic and therapeutic) potential as a prognostic marker, as well as an anti-metastatic target. The distinct advantages offered by the VGSC include especially (1) its embryonic nature, demonstrated most clearly for the predominant neonatal Nav1.5 expression in breast and colon cancer, and (2) the specifically druggable persistent current that VGSCs develop under hypoxic conditions, as in growing tumours, which promotes invasiveness and metastasis.

show abstract

Section: Clinical Studiesmentioning

confidence: 99%

Section: Clinical Studiesmentioning

confidence: 99%

In Vivo Evidence for Voltage-Gated Sodium Channel Expression in Carcinomas and Potentiation of Metastasis

Djamgoz

Fraser

Brackenbury

2019

Cancers

View full text Add to dashboard Cite

show abstract

“…SAHA-mediated downregulation of Ku70 and Ku80 protein was seen in colon cancer cells, suggesting implication of non-homologous end-joining (NHEJ) DNA repair pathway in the radiosensitization 15 . As with SAHA, increased efficacy by combination treatment with VPA and photon irradiation has been reported in preclinical and/or clinical setting 25 , 26 , 32 . In consistent with the previous results, enhanced radiation sensitivity by VPA was also seen in our study with HCC cells.…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid Sensitizes Hepatocellular Carcinoma Cells to Proton Therapy by Suppressing NRF2 Activation

Choi

Shin

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Although efficacy of combined histone deacetylase (HDAC) inhibitors and conventional photon radiotherapy is being tested in clinical trials, their combined effect with proton beam radiotherapy has yet to be determined. Here, we compared combined effect of valproic acid (VPA), a class I and II HDAC inhibitor and antiepileptic drug with proton and photon irradiation in hepatocellular carcinoma (HCC) cells in vitro and in vivo. We found that VPA sensitized more Hep3B cells to proton than to photon irradiation. VPA prolonged proton-induced DNA damage and augmented proton-induced apoptosis. In addition, VPA further increased proton-induced production of intracellular reactive oxygen species and suppressed expression of nuclear factor erythroid-2-related factor 2 (NRF2), a key transcription factor regulating antioxidant response. Downregulation of NRF2 by siRNA transfection increased proton-induced apoptotic cell death, supporting NRF2 as a target of VPA in radiosensitization. In Hep3B tumor xenograft models, VPA significantly enhanced proton-induced tumor growth delay with increased apoptosis and decreased NRF2 expression in vivo. Collectively, our study highlights a proton radiosensitizing effect of VPA in HCC cells. As NRF2 is an emerging prognostic marker contributing to radioresistance in HCC, targeting NRF2 pathway may impact clinical outcome of proton beam radiotherapy.

show abstract

“…In recent years, a growing list of retrospective analyses has demonstrated that glioma patients exposed to VPA have an improvement of the survival time by several months (Weller et al, 2011;Weller et al, 2013;Guthrie and Aljamel, 2013;Karkhof et al, 2013;Reddy et al, 2015). In the prospective randomized study of Stupp et al (2005), patients with newly diagnosed glioblastoma were treated with radiotherapy alone or radiotherapy plus temozolomide.…”

Section: Efficacy Of Antiepileptic Drugs In Tumoral Epilepsymentioning

confidence: 99%

Anticonvulsant therapy in brain-tumor related epilepsy

Fröscher

Kirschstein

Rösche

2016

Journal of Epileptology

View full text Add to dashboard Cite

SummaryBackground. The lifetime risk of patients with brain tumors to have focal epileptic seizures is 10-100%; the risk depends on different histology. Specific guidelines for drug treatment of brain tumor-related seizures have not yet been established.Aim. This review addresses the special aspects of antiepileptic drug (AED) therapy in brain tumor-related epilepsy.Methods. We analyzed the literature up to December 2015.Results. Based on current evidence the management of tumor-related seizures does not differ substantially from that applied to epilepsies from other etiologies. Therefore, the choice of an AED is based, above all, on tolerability and pharmacokinetic interactions with chemotherapeutic drugs. Levetiracetam is recommended by many authors as first-line therapy in brain tumor-related epilepsy. Due to the possibility of interactions, the combination of enzyme-inducing AEDs and chemotherapeutic drugs, is usually not recommended as a first choice. Currently there is no evidence that prophylactic prescription of long-term AEDs in brain tumor-patients who did not present with seizures is justified. Because of the high risk of recurrence, however, AED treatment should be strongly considered after a single brain tumor-related seizure. The decision to withdraw AEDs must carefully consider the risk of seizure recurrence.Conclusion. At present levetiracetam is the preferred drug in brain tumor-related epilepsy, especially when drug interactions need to be avoided. In the future we hope to acquire more targeted drugs against this disorder by uncovering its pathogenesis.

show abstract

Antiepileptic drug use improves overall survival in breast cancer patients with brain metastases in the setting of whole brain radiotherapy

Cited by 23 publications

References 31 publications

In Vivo Evidence for Voltage-Gated Sodium Channel Expression in Carcinomas and Potentiation of Metastasis

In Vivo Evidence for Voltage-Gated Sodium Channel Expression in Carcinomas and Potentiation of Metastasis

Valproic Acid Sensitizes Hepatocellular Carcinoma Cells to Proton Therapy by Suppressing NRF2 Activation

Anticonvulsant therapy in brain-tumor related epilepsy

Contact Info

Product

Resources

About