Seizures and cancer: drug interactions of anticonvulsants with chemotherapeutic agents, tyrosine kinase inhibitors and glucocorticoids.

Patients with cancer commonly experience seizures. Combined therapy with anticonvulsant drugs (AEDs) and chemotherapeutic drugs or tyrosine kinase inhibitors carries inherent risks on drug-drug interactions (DDIs). In this review, pharmacokinetic studies of AEDs with chemotherapeutic drugs, tyrosine kinase inhibitors, and glucocorticoids are discussed, including data on maximum tolerated dose, drug clearance, elimination half-life, and organ exposure. Enzyme-inducing AEDs (EIAEDs) cause about a 2-fold to 3-fold faster clearance of concurrent chemotherapeutic drugs metabolized along the same pathway, including cyclophosphamide, irinotecan, paclitaxel, and teniposide, and up to 4-fold faster clearance with the tyrosine kinase inhibitors crizotinib, dasatinib, imatinib, and lapatinib. The use of tyrosine kinase inhibitors, particularly imatinib and crizotinib, may lead to enzyme inhibition of concurrent therapy. Many of the newer generation AEDs do not induce or inhibit drug metabolism, but they can alter enzyme activity by other drugs including AEDs, chemotherapeutics and tyrosine kinase inhibitors. Glucocorticoids can both induce and undergo metabolic change. Quantitative data on changes in drug metabolism help to apply the appropriate dose regimens. Because the large individual variability in metabolic activity increases the risks for undertreatment and/or toxicity, we advocate routine plasma drug monitoring. There are insufficient data available on the effects of tyrosine kinase inhibitors on AED metabolism.

Seizures in oligodendroglial tumors.

Epilepsy develops in more than 70-90% of oligodendroglial tumors and represents a favorable indicator for long-term survival if present as the first clinical sign. Presence of IDH1 mutation is frequently associated with seizures in oligodendrogliomas, next to alterations of glutamate and GABA metabolism in the origin of glioma-associated epilepsy. Treatment by surgery or radiotherapy results in seizure freedom in about two-thirds of patients, and chemotherapy to a seizure reduction in about 50%. Symptomatic anticonvulsive therapy with levetiracetam and valproic acid as monotherapy are both evidence-based drugs for the partial epilepsies, and their effective use in brain tumors is supported by a large amount of additional data. Pharmacoresistance against anticonvulsants is more prevalent among oligodendrogliomas, occurring in about 40% despite polytherapy with two anticonvulsants or more. Toxic signs of anticonvulsants in brain tumors involve cognition, bone marrow and skin. Previous neurosurgery, radiation therapy or chemotherapy add to the risks of cognitive dysfunction.

[Practice guideline 'Management of patients with mild traumatic head/brain injury' in the Netherlands]. / Richtlijn 'Licht traumatisch hoofd-hersenletsel' in de praktijk.

OBJECTIVE: To evaluate the effect of the revised practice guideline 'Management of patients with mild traumatic head/brain injury' (MHI) in the Netherlands using the number of CT scans of the cerebrum, number of hospital admissions, and the number of intracranial traumatic findings on CT scan. DESIGN: Retrospective before-and-after study. METHOD: A structured chart review over the 3-month period considerable time after implementation of the MHI guideline (study period) was compared with the 3-month-period before its introduction (control period). Both children and adults were included. Primary outcome measures were the percentage of hospital admissions and percentage of cerebrum CT scans in patients with MHI. Secondary outcome measures were traumatic findings on CT scan, neurosurgical intervention and adherence to the guideline. RESULTS: During the study and control periods, respectively 1063 and 1026 patients with MHI attended the emergency department of the study centre. During the study period a CT scan was carried out in 34.2% of patients, significantly more than in the control period 18.8%; p < 0.01). The percentage of admissions also increased from 13.8% to 18.2% (p = 0.01). The differences between the two periods were mainly in adults and in children aged 6 and older. There was no significant change in traumatic intracranial findings or neurosurgical interventions. Adherence to the guideline in regard to hospitalization (81.7% guideline adherence) and CT brain imaging (88.3% guideline adherence) was reasonably high. CONCLUSION: After introduction of the current MHI guideline in the Netherlands, percentages of both hospitalization and CT of cerebrum have increased significantly. It was expected that the guideline would result in decreases of this percentages. This increase does not seem to be related to more or serious head/brain injury.