Antiepileptic Treatment in Paediatric Oncology - An Interdisciplinary Challenge

Abstract

Epileptic seizures are a common and clinically relevant problem in paediatric oncology. Attributable to the heterogeneity of this group of patients and a number of possible comorbidities antiepileptic treatment in paediatric oncology poses a number of diagnostic and therapeutic challenges. This requires a close interdisciplinary approach to the seizing child or adolescent. A prompt and detailed diagnostic work-up is needed in every case in order to establish the diagnosis and, equally important, to detect secondary aetiological factors, e. g. epileptogenic drugs or any acute underlying pathology, such as metabolic or toxic encephalopathies, CNS-infections or cerebrovascular events. This might offer the opportunity for a specific causative treatment and thus prevent unnecessary long-term antiepileptic drug (AED) treatment. If AED treatment is initiated several aspects have to be taken into account. Most importantly, AEDs and chemotherapeutic drugs (CTDs) may interact. Depending on the comedication this may result in reduced tumour or seizure control or unexpected toxicity of AEDs or CTDs. Understanding these interactions will allow to anticipate clinically relevant adverse effects. AED may be further complicated by side-effects, some of them of particular concern for children or adolescents, such as cognitive effects, myelotoxicity, serious rashes, endocrinological disturbances, and many more. Beside critically questioning the need for AED treatment it is therefore important to prefer AED with a good safety-profile in this population. Enzyme-inducing and inhibiting AED should be avoided if possible. Preliminary studies indicate that gabapentin and levetiracetam may provide good options in terms of efficacy and safety. However, more properly designed clinical studies are warranted to raise the level of evidence for robust clinical recommendations. Until that time, clinicians will need to continue to question current policies and adapt their daily practice to evolving scientific data.

Zusammenfassung

Epileptische Anfälle stellen in der pädiatrischen Onkologie ein häufiges und klinisch relevantes Problem dar. Bedingt durch die Heterogenität der betroffenen Patientengruppe und einer Vielzahl von möglichen Komorbiditäten sind sowohl das diagnostische Vorgehen als auch die antikonvulsive Therapie eine besondere Herausforderung, die ein interdisziplinäres Vorgehen erfordert. Diagnostisch sind neben einer Vielzahl von potenziell epileptogenen Medikamenten vor allem akute Begleiterkrankungen im Verlauf der Krebstherapie zu berücksichtigen, die ursächlich für das Auftreten von Anfällen sein können. Beispiele sind metabolische oder toxische Encephalopathien, ZNS-Infektionen oder auch zerebrovaskuläre Ereignisse. Da diese zum Teil lebensbedrohlichen Erkrankungen zum Teil kausal behandelbar sind, erfordert jedes anfallsverdächtige Ereignisses eine rasche und umfassende Abklärung. So können spezifische Ursachen erkannt und behandelt sowie unnötige antikonvulsive Langzeittherapien vermieden werden. Besteht eine Therapieindikation zur antikonvulsiven Dauertherapie so liegt die Schwierigkeit primär in einer Vielzahl von Komedikationen und damit der Gefahr von Wechselwirkungen insbesondere zwischen Antikonvulsiva und Chemotherapeutika. Das Wissen um diese Wechselwirkungen ist wichtig, da sowohl die Prognose der Krebserkrankung, als auch die der Epilepsie hierdurch nennenswert beeinflusst werden kann. Zusätzlich erschweren eine Reihe onkologisch relevanter Nebenwirkungen die Entscheidungsfindung bei der Auswahl der Antiepileptika. Dies betrifft z. B. kognitive Nebenwirkungen, myelotoxische Wirkungen, Dermatosen, endokrinologische Effekte und andere mehr. Neben der kritischen Indikationsstellung einer antikonvulsiven Therapie gilt es daher bevorzugt Antikonvulsiva einzusetzen, die ein günstiges Nebenwirkungsprofil in dieser Patientengruppe haben und zusätzlich durch fehlende Enzyminduktion bzw. Inhibition gekennzeichnet sind. Nach aktuellem Kenntnisstand scheinen hier vor allem Gabapentin und Levetiracetam günstige Optionen darzustellen. Angesichts einer sehr schlechten Studienlage sind jedoch weitere klinische Studien zu diesen wichtigen Fragestellungen dringend zu fordern, aktuelle Therapieregime kritisch zu hinterfragen und gegebenenfalls der aktuellen Datenlage anzupassen.

Key words

cancer - seizures - antiepileptic drugs - drug interaction

Schlüsselwörter

Krebs - Krampfanfälle - Antiepileptika - Wechselwirkungen

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