Neurologische Nebenwirkungen von Zytostatika

Zusammenfassung

Die Zahl der jährlich mit einer zytostatischen Chemotherapie behandelten Patienten nimmt vor dem Hintergrund einer steigenden Inzidenz und Prävalenz von Tumorerkrankungen kontinuierlich zu. Bedingt durch bessere supportive Therapien insbesondere hämatologischer Nebenwirkungen und einer gesteigerten Lebenserwartung der Patienten rücken neurologische Therapiefolgen zunehmend in den Vordergrund. Es ist bemerkenswert, dass neurotoxische Phänomene, nach hämatologischen- bzw. gastroenterologischen Toxizitäten, trotz des postmitotischen Zustands von Nervenzellen zu den häufigsten Nebenwirkungen vieler Zytostatika zählen. Diese pathogenetisch schlecht verstandenen unerwünschten Arzneimittelwirkungen (UAW) stellen ein erhebliches medizinisches Problem dar, da sie einerseits häufig eine Dosislimitierung und damit letztlich eine suboptimale Tumortherapie bedingen und andererseits zu einer erheblichen, oft langanhaltenden Einschränkung der Lebensqualität für die Betroffenen führen. Trotz des exakt definierten und vorab bekannten Schädigungszeitpunkts gibt es kaum validierte therapeutische bzw. präventive Ansätze für neurotoxische Nebenwirkungen von Zytostatika. Die Kenntnis Chemotherapie-induzierter neurologischer Pathologien im peripheren und zentralen Nervensystem ist, angesichts der Vielzahl möglicher Symptome, zur differenzialdiagnostischen Abgrenzung von anderen Erkrankungsentitäten von hoher praktischer Relevanz. Um zunehmend komplexeren Behandlungsprotokollen und einer steigenden Zahl zytostatischer Medikamente Rechnung zu tragen, werden im Rahmen dieser Übersichtsarbeit relevante neurologische Nebenwirkungen gängiger Zytostatika im peripheren und zentralen Nervensystem dargestellt und, sofern verfügbar, mögliche therapeutische Strategien aufgezeigt. Konkret widmet sich der erste Teil dieser Übersicht Nebenwirkungen im peripheren Nervensystem welche durch Substanzen aus der Gruppe der Platinverbindungen (Cisplatin, Carboplatin, Oxaliplatin), Vincaalkaloide (Vincristin), Taxane (Paclitaxel, Docetaxel), Proteasominhibitoren (Bortezomib) und Antikörperkonjugate (Brentuximab-Vedotin) hervorgerufen werden. Der zweiten Teil dieser Arbeit fokussiert sich auf neurotoxische UAW im zentralen Nervensystem, hervorgerufen durch Medikamente aus der Gruppe der Antimetabolite (Methotrexat, 5-Fluoruracil, Cytarabin, Fludarabin), Alkylanzien (Ifosfamid), Platin-Verbindungen (Cis-Platin), Vincaalkaloide (Vincristin), Rezeptor-Tyrosinkinase Inhibitoren (Imatinib, Sorafenib, Sunitinib) und Biologicals (Bevacizumab). Zuletzt wird im dritten Teil auf das ätiologisch noch umstrittene Krankheitsbild der Chemotherapie-induzierten kognitiven Defizite eingegangen.

Abstract

With an increasing incidence of malignancies, the number of patients treated with cytostatic chemotherapy is rising continuously. Neurological sequelae of tumor therapy are a growing concern as improved therapy protocols increase the life expectancy of patients. Despite the postmitotic state of neurons, neurotoxic phenomena are amongst the most common side effects of many cytostatic drugs, second only to hematological or gastroenterological toxicities. Chemotherapy-induced neurotoxic phenomena represent a medical problem as they can be dose limiting, thus preventing optimal therapy, and lead to long-lasting limitations in quality of life. There are hardly any validated therapeutic or preventive approaches to neurotoxic side effects of cytostatic drugs. In view of the large number of possible neurotoxic symptoms, knowledge of chemotherapy-induced neurological pathologies in the central and peripheral nervous system is of practical relevance for making a differential diagnosis.

In the context of ever more complex treatment protocols and increasing number of cytostatic drugs, we review the neurological side effects of chemotherapeutic drugs in general use in the peripheral and central nervous system and discuss potential therapeutic strategies. In the first part, this review focuses on side effects in the peripheral nervous system of platinum-based antineoplastic drugs (cisplatin, carboplatin, oxaliplatin), vincaalcaloids (vincristine), taxanes (paclitaxel, docetaxel), proteasome inhibitors (bortezomib) and biologicals (brentuximab-vedotin). The second part is dedicated to neurotoxic side effects in the central nervous system induced by antimetabolites (methotrexate, 5-fluoruracil, cytarabine, fludarabine), alkylating agents (ifosfamide), platinum-based antineoplastic drugs (cisplatin), vincaalcaloids (vincristine), receptor tyrosine kinase inhibitors (imatinib, sorafenib, sunitinib) and biologicals (bevacizumab). In the third part of this review we summarize current data on the illness entity of chemotherapy-induced cognitive impairment, whose etiology continues to be controversial.

Schlüsselwörter

Chemotherapie induzierte Neuropathie - neuropathischer Schmerz - Neurotoxizität - Post chemotherapy ­cognitive impairment - posteriores reversibles Enzephalopathie-Syndrom

Keywords

chemotherapy induced neuropathy - neuropathic pain - neurotoxicity - post chemotherapy ­cognitive impairment - posterior reversible ­encephalopathy syndrome

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