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To the Editor:
Jaeckle et al.1 compared the survival rates in glioblastoma patients who used enzyme-inducing anticonvulsants (EIAC) to those of patients who did not. The authors performed a careful—albeit retrospective—pooled subgroup analysis of 3 chemotherapy trials. As they state, their results are counterintuitive. However, there are many limitations.
It is unclear which drugs were prescribed. The study period and location suggest that phenytoin (PHT) was the most popular compound. However, PHT and dexamethasone exert a reciprocal pharmacokinetic interaction, mutually lowering the efficacy of the other drug due to concurrent protein binding competition and hepatic enzyme induction.2 It is counterintuitive to conclude that patients would live longer because the administered drugs act less.
Of 605 patients, 71.4% received EIAC, 2.3% were on nonenzyme-inducing compounds, and 26.2% did not take any antiepileptic drug (AED). Although longitudinal data are lacking, only 14.5% experienced seizures. This corresponds to a lower epilepsy prevalence than reported in similar populations,3 and reflects the policy of prophylactic treatment. It was found that this treatment was not effective in a meta-analysis of studies where EIAC were almost exclusively administered.4 This meta-analysis also noted the frequent AED subtherapeutic levels and consistent risks of unwanted side effects. In the absence of drug serum levels, it is difficult to assume that EIAC contributed to improved survival.
The null hypothesis of shorter survival following increased chemotherapy metabolism …
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