Diagnostik und Therapie Chemotherapie-induzierter Polyneuropathien: Update 2016

Zusammenfassung

Die Chemotherapie-induzierte Neuropathie (CIPN) ist eine häufige Folgeerscheinung einer Tumortherapie mit Zytostatika wie Platinderivaten, Vincaalkaloiden, Taxanen, sogenannten „small molecules“ sowie modernen Antikörper-basierten Therapien. Als Folge der immer effektiver werdenden Chemotherapieformen und der höheren Langzeitüberlebensrate ist die Inzidenz der CIPN in den letzten Jahren stetig steigend. Die Ursachen und Mechanismen der CIPN auf zellulärer und molekularer Ebene sind dabei vielfältig. Beteiligt sind sowohl inflammatorische Mediatoren, Störungen der neuronalen Ionenkanalfunktion sowie Veränderungen der intrazellulären Signaltransmission. Weitere Mechanismen wie DNA-Schädigung, Einschränkung der DNA-Reparaturkapazität, mitochondriale Störungen, reaktive Sauerstoffspezies und ektope Aktivierung von Nozizeptoren begünstigen das Auftreten neuropathischer Schmerzsyndrome. Strukturelle Störungen der Spinalganglien und sensiblen Nerven führen zu vorwiegend sensorischen Störungen, wie Par-, Dys- und Hypästhesien mit der Folge einer deutlichen Einschränkung der Lebensqualität aber auch einem häufigen Abbruch einer notwendigen und effektiven Tumortherapie. Die Diagnosestellung erfolgt überwiegend klinisch, das Assessment zielt bei Patienten-orientierten Fragebögen auf die Erhebung der Störungen der verschiedenen Nervenfasertypen. Eine kausale Therapie ist bisher nicht möglich, häufig wird die Therapie beendet oder die Dosis der Chemotherapie reduziert. Nichtsdestotrotz sind symptomatische Therapiemöglichkeiten zur Therapie der assoziierten neuropathischen Schmerzen vorhanden. Diese Übersichtsarbeit soll die aktuellen Erkenntnisse der Mechanismen die zur CIPN führen beleuchten, die Diagnosestellung und Therapie der täglichen Praxis zeigen, sowie laufende Entwicklungen der kommenden Therapieformen der CIPN darstellen.

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition in patients undergoing treatment with commonly used agents such as platinum compounds, vinca alcaloids, taxanes, small molecules and antibody-based therapies. The incidence of CIPN is increasing as a consequence of better cancer treatments becoming available and increasing use of chemotherapy, and because it is a more frequently occurring side-effect with use of new chemotherapeutics. The mechanisms underlying this condition are diverse, and include an array of molecular and cellular contributions. Processes influenced by CIPN include increased expression of inflammatory mediators, changes in ion channels and neurotransmission, as well as changes in intracellular signaling and structures. Structural deficits in dorsal root ganglia and sensory nerves cause symptoms such as sensory loss, paresthesia, dysesthesia, numbness as well as neuropathic pain that result in patient suffering and also limit the therapeutic efficiency with a severe impairment of quality of life. DNA damage, alterations in cellular system repairs, mitochondrial changes, increased intracellular reactive oxygen species, glutamate signaling, MAP-kinases and nociceptor ectopic activation are among the events that trigger the onset of peripheral neurotoxicity and neuropathic pain. The diagnosis of CIPN is made principally on clinical grounds, and it is characterized by predominantly sensory symptoms. CIPN assessment relies mainly on patient-oriented questionnaires, but an international effort is ongoing to assess reliable and objective means to assess small and large fiber impairment. If CIPN occurs, the only effective strategies are dose reduction or discontinuation of chemotherapy. However, symptomatic treatment of mainly neuropathic pain symptoms is available and effective. The purpose of this review is to examine the basic mechanisms of neuropathy and currently available treatment options in the context of CIPN.

Schlüsselwörter

Chemotherapie - Neuropathischer Schmerz - Polyneuropathie

Keywords

chemotherapy - neuropathic pain - polyneuropathy

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