Treating seizures in patients with brain tumors: drug interactions between antiepileptic and chemotherapeutic agents

Vecht, Charles J.; Wagner, G; Wilms, Erik B

doi:10.1053/j.seminoncol.2003.11.030

Cited by 81 publications

(45 citation statements)

References 19 publications

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“…VPA, in contrast, is an inhibitor of cytochrome P450 isoenzymes and the concentration of several chemotherapeutic drugs, e.g. nitrosureas and etoposide, can be increased due to reduced elimination (15,27,28). The metabolism of small molecule kinase inhibitors is also frequently influenced by EIAED and VPA.…”

Section: Discussionmentioning

confidence: 99%

Intravenous and oral levetiracetam in patients with a suspected primary brain tumor and symptomatic seizures undergoing neurosurgery: the HELLO trial

et al. 2011

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BACKGROUND: Levetiracetam (LEV) is a newer anticonvulsant with a favorable safety profile. There seem to be no relevant drug interactions, and an intravenous formulation is available. Therefore, LEV might be a suitable drug for the perioperative anticonvulsive therapy of patients with suspected brain tumors undergoing neurosurgery. METHODS: In this prospective study (NCT00571155) patients with suspected primary brain tumors and tumor-related seizures were perioperatively treated with oral and intravenous LEV up to 4 weeks before and until 4 weeks after a planned neurosurgical procedure. FINDINGS: Thirty patients with brain tumor-related seizures and intended neurosurgery were included. Three patients did not undergo the scheduled surgery after enrollment, and two patients were lost to follow-up. Therefore, 25 patients were fully evaluable. After initiation of therapy with LEV, 100% of the patients were seizure-free in the pre-surgery phase (3 days up to 4 weeks before surgery), 88% in the 48 h post-surgery phase and 84% in the early follow-up phase (48 h to 4 weeks post surgery). Treatment failure even after dose escalation to 3,000 mg/day occurred in three patients. No serious adverse events related to the treatment with LEV occurred. CONCLUSION: Our data show the feasibility and safety of oral and intravenous LEV in the perioperative treatment of tumor-related seizures. Although this was a single arm study, the efficacy of LEV appears promising. Considering the side effects and interactions of other anticonvulsants, LEV seems to be a favorable option in the perioperative treatment of brain tumor-related seizures.

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Section: Discussionmentioning

confidence: 99%

Intravenous and oral levetiracetam in patients with a suspected primary brain tumor and symptomatic seizures undergoing neurosurgery: the HELLO trial

et al. 2011

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“…In a previous report a signiWcant induction of cyclophosphamide and thiotepa metabolism by phenytoin was described [20]. When seizure control is necessary in patients receiving concomitant chemotherapy, drugs that do not inXuence the hepatic cytochrome P450 enzyme system (gabapentin and levetiracetam) are to be preferred [21].…”

Section: Discussionmentioning

confidence: 99%

Carbamazepine induces bioactivation of cyclophosphamide and thiotepa

Ekhart

Rodenhuis

Beijnen

et al. 2008

Cancer Chemother Pharmacol

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Purpose We report a patient with metastatic breast cancer who received three cycles of high-dose chemotherapy with cyclophosphamide [1,000 mg/(m 2 day)], thiotepa (80 mg/ (m 2 day) and carboplatin (dose calculated based on modiWed Calvert formula with 3.25 mg min/ml as daily target AUC) over 4 days, followed by peripheral blood progenitor cell support. During the Wrst two cycles the patient concomitantly used carbamazepine for the treatment of epilepsy. Due to severe nausea and vomiting the patient was unable to ingest carbamazepine; therefore, this was discontinued after the second cycle. Methods Blood samples were drawn on 2 days (day 1 and 2, 3 or 4) of each cycle and plasma levels of cyclophosphamide, its active metabolite 4-hydroxycyclophosphamide, thiotepa, its main, active metabolite tepa and carboplatin were determined. Results Exposure to 4-hydroxycyclophosphamide and tepa on day 1 was increased in the presence of carbamazepine (58 and 75%, respectively), while exposure to cyclophosphamide and thiotepa was reduced (40 and 43%, respectively). ConclusionSince increased exposure to the active metabolites is associated with an increased risk of toxicity, it is important to be aware of this drug-drug interaction.

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“…As mentioned earlier, prophylactic use of anticonvulsant drugs is not indicated in patients without history of seizures (12). Enzyme inducers antiepileptic drugs should be avoided as they interact with commonly used cytotoxic agents and dexamethasone, having the potential to reduce their efficacy (238). Valproic acid is an enzyme inhibitor that may increase therapeutic levels of antineoplastic agents.…”

Section: Seizuresmentioning

confidence: 99%

Current Standards of Care in Glioblastoma Therapy

et al. 2017

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Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Regardless of ideal multidisciplinary treatment, including maximal surgical resection, followed by radiotherapy plus concomitant and maintenance temozolomide (TMZ), almost all patients experience tumor progression with nearly universal mortality and a median survival of less than 15 months. The addition of bevacizumab to standard treatment with TMZ revealed no increase in overall survival (OS) but improved progression-free survival (PFS). In newly diagnosed GBM, methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter has been shown to predict response to alkylating agents, as well asgnosis. Therefore, MGMT promoter status may have a crucial role in the choice of single modality treatment in fragile elderly population. No standard of care is established in recurrent or progressive GBM. Treatment alternatives may include supportive care, surgery, re-irradiation, systemic therapies, and combined modality therapy. Despite numerous clinical trials, the identification of effective therapies is complex because of the lack of appropriate control arms, selection bias, small sample sizes, and disease heterogeneity. Tumor-treating fields plus TMZ represent a major advance in the field of GBM therapy, and should be Standards of Care in Glioblastoma Therapy 198 considered for patients with newly diagnosed GBM with no contraindications. As a disease with such a poor prognosis, treatment of GBM should go beyond improving survival and aim at preserving and even improving the quality of life of both the patient and the caregiver.

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Treating seizures in patients with brain tumors: drug interactions between antiepileptic and chemotherapeutic agents

Cited by 81 publications

References 19 publications

Intravenous and oral levetiracetam in patients with a suspected primary brain tumor and symptomatic seizures undergoing neurosurgery: the HELLO trial

Intravenous and oral levetiracetam in patients with a suspected primary brain tumor and symptomatic seizures undergoing neurosurgery: the HELLO trial

Carbamazepine induces bioactivation of cyclophosphamide and thiotepa

Current Standards of Care in Glioblastoma Therapy

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