Epileptic seizures develop in cancer patients for many reasons.  Seizures are a common symptom of brain tumours, found in between 25% and 40% of cases of both primary brain tumours and brain metastases; they may be the first noticeable symptoms of primary tumours. Less frequently, they may arise from metabolic problems or CNS infections or as side effects of chemotherapy drugs. Furthermore, seizures will remain a problem in cancer patients with pre-diagnosed epilepsy. Although epilepsy is very often well controlled with drug therapy, the presence of cancer and epileptic-like seizures in the same patient complicates the treatment of both conditions.  Odysseas Kargiotis of the University of Ioannina, Ioannina, Greece, and his co-workers have published a review of literature concerning the epidemiology, pathology and drug treatment of epilepsy or epileptic-like seizures in patients also diagnosed with cancer.

Several studies have reported that seizures are more prevalent in patients with low-grade and slow-growing brain tumours than in the highest-grade glioblastoma multiforme. Dysembryoplastic neuroepithelial tumours and angliogliomas are the most likely brain tumours to cause seizures, with an incidence of over 90% for each type, while meningiomas cause seizures only rarely. Several mechanisms through which brain tumours might trigger epilepsy have been proposed, the most widely-studied of which is the alteration of the expression and activity of receptors in brain tissue that respond to neurotransmitters such as GABA and glutamate.

Physicians commonly prescribe anti-epileptic drugs including phenobarbital, phenytoin, and valproic acid as prophylactics to patients who have been diagnosed with brain tumours without experiencing seizures. However, Kargiotis and his co-workers reported several recent meta-analyses of clinical trial data that failed to show any benefit of such prophylactic treatment, regardless of tumour type or grade, except perhaps in the immediate post-operative period. Similar results were observed in patients with primary brain tumours and in those with brain metastases. One study reported good results with the anticonvulsant levetiracetam used as a short-term post-operative prophylactic.

There is a wide range of anticonvulsant drugs available for clinicians treating patients with epilepsy. Treatment of cancer patients with induced seizures, or of patients with pre-existing epilepsy who are later diagnosed with cancer, is complicated by interactions between anti-epileptic medication and chemotherapy drugs. Many anticonvulsants are active and non-toxic only in a narrow concentration range (they have a narrow therapeutic window) and the co-prescription of drugs that alter their pharmacokinetics may seriously affect their activity. Conversely, co-prescription of anti-epileptic drugs may affect the pharmacokinetics and activity profiles of some anti-cancer agents. Several studies have highlighted levetiracetam as an anticonvulsant that causes few problems in combination with chemotherapeutic drugs.

An ideal treatment for epilepsy in cancer patients would be a drug that combines both anticonvulsant and chemotherapeutic properties. The only anticonvulsant to have any documented potential activity against cancer is valproic acid, which has been in clinical use against epilepsy for decades and is also prescribed for bipolar disorder. This drug is a histone deacetylase inhibitor which modulates cellular processes linked to cancer including proliferation, apoptosis, and cell migration. Valproic acid also appears to show some activity in sensitising tumours to radiotherapy, and levetiracetam may sensitise tumour cells to temozolomide.

Kargiotis and his co-workers conclude by presenting an algorithm that should prove useful in the complex task of selecting an anticonvulsive drug for cancer patients. They do not recommend anti-convulsive prophylaxis except in the immediate post-operative period, and propose that, unless or until a drug that is effective at controlling both conditions is developed, tolerability and absence of interactions with anti-cancer drugs will be important considerations for this patient group.

Article:

Kargiotis, O., Markoula, S. and Kyritsis, A.P. (2011). Epilepsy in the cancer patient. Cancer Chemother Pharmacol 67: 489–501. DOI: 10.1007/s00280-011-1569-0