Clinical and Translational Oncology
Choice of antiepileptic drugs aects the outcome in cancer patients
· D. San‑Juan
· K. Salmeron
· C. Boyzo
· N. Lorenzana‑Mendoza
Received: 23 March 2018 / Accepted: 9 May 2018
© Federación de Sociedades Españolas de Oncología (FESEO) 2018
Background Seizures in cancer patients may occur as a result of CNS primary or metastatic tumor, brain surgery, vascular
disease, pharmacologic treatment (including chemotherapy), radiation therapy, or metabolic disorders. The aims of the study
were to a) determine whether seizures in cancer patients have prognostic implications and b) study patient outcome based
on the antiepileptic drug used.
Method This is a prospective comparative study that included adult cancer patients with and without seizures from May
2010 to November 2016 seen by the neuro-oncology unit at a cancer referral center. Variables included age, gender, oncologic
characteristics, seizure features, treatment, and outcome. Parametric and non-parametric tests were used to compare groups,
and Kaplan–Meier curves with the log-rank test were used to analyze survival. Cox multivariate regression tests were used
to describe survival and compare groups.
Results A total of 823 patients were included; 419 (51%) patients had at least one seizure and were compared with 404 (49%)
who did not experience seizures. Of the seizure group, 53% had brain metastases, 36% did not have a brain tumor, and 11%
had a primary brain tumor. No survival diﬀerences were noted among patients with brain metastases or primary tumor with
or without seizures. In the seizure group, 249 (59%) required only one antiepileptic drug, whereas 134 (32%) required 2
or more. A better overall survival was identiﬁed for patients prescribed carbamazepine (p = 0.02), lamotrigine (p = 0.015),
levetiracetam (p = 0.03), and valproic acid (p = 0.009).
Conclusions Patients with primary or metastatic brain tumors have the same overall survival with or without seizures. How-
ever, patients with seizures not treated with antiepileptics exhibit worse overall survival.
Keywords Seizure · Cancer · Antiepileptic · Drug · Prognosis · Metastases
Epilepsy is a common manifestation of patients with can-
cer. For example, one-third of patients with meningiomas,
greater than two-thirds of patients with gliomas, and 60%
of patients with brain metastasis have seizures [1–4]. The
overall incidence of tumor-associated epilepsy varies from
35 to 90% [5, 6].
Seizures (Sz) in cancer patients may occur as a result of
CNS primary (pCNS) or metastatic (CNSm) tumors, brain
surgery, vascular disease, pharmacologic treatment (includ-
ing chemotherapy), radiation therapy, or metabolic disor-
ders [7, 8]. Seizures have been questionably identiﬁed as
a positive prognostic factor in patients with glioma [1–4,
9] and scarcely studied in brain metastases. Furthermore,
seizure control is an important challenge in the clinical
management of low-grade gliomas and has been proposed
as a complementary marker of tumor response [5, 6, 10].
Clinicians should be aware of pharmacokinetic interactions
of chemotherapeutic agents and antiepileptic drugs (AEDs)
when choosing an adequate AED [1, 11, 12]. In addition,
clinicians should be aware that administering prophylactic
AEDs is not generally justiﬁed [7, 8, 13].
* B. Cacho-Diaz
Neuroscience Unit, Neuro-oncology Service, Instituto
Nacional de Cancerología, Avenida San Fernando 22 Col,
Sección XVI, Tlalpan, Mexico City 14080, Mexico
Clinical Research Department, National Institute
of Neurology and Neurosurgery, Mexico City, Mexico