Nebenwirkungsmanagement von Afatinib

Zusammenfassung

Die neuen, oral verabreichten Zytostatika vom Typ der Tyrosinkinasehemmstoffe (TKI) z. B. gegen den Wachstumsfaktor-Rezeptor EGFR/HER2 (Epidermal growth factor receptor) sind mit typischen Nebenwirkungen wie Hautveränderungen und Diarrhöen assoziiert. Auch wenn diese klinisch meist mild und nicht vital gefährdend sind, kann die psychische Belastung für den Patienten erheblich sein und bis zum Therapieabbruch führen. Durch die einfache orale Administration kommen EGFR-TKI aus den Fachkliniken zunehmend in den Bereich der niedergelassenen Ärzte. Daher soll dieser Review dem niedergelassenen Arzt konkrete Handlungsanweisungen zur Bewertung und Therapie der häufigsten Nebenwirkungen an die Hand geben. Mittlerweile sind mehrere TKI zugelassen, weitere, wie beispielsweise Afatinib, befinden sich in späten Stadien der klinischen Prüfung. Afatinib ist eine Substanz der neuesten Generation (irreversible TKI) mit breiterem TKI-Spektrum (Erb familyblocker) und den klassentypischen Nebenwirkungen.

Gastrointestinale Nebenwirkungen wie Durchfall sind insbesondere zu Behandlungsbeginn häufig, können aber analog zu Chemotherapeutika nach dem hier vorgestellten Schema auf Basis von Loperamid und ggf. Octreotid behandelt werden. Stomatitis/Mukositis können durch gezielte Pflege und Kühlung gelindert werden. Für akneiforme Dermatitiden ist in Abhängigkeit vom Schweregrad eine gezielte topische oder systemische Antibiose in Verbindung mit weiteren lokalen Maßnahmen sinnvoll. Fatigue ist bei Afatinib eine eher seltener auftretende, dennoch ernst zu nehmende Nebenwirkung.

Abstract

Tyrosine kinase inhibitors (TKI) of growth factor receptors such as EGFR/HER2, a new generation of anti-tumor drugs, are usually associated with typical side effects such as cutaneous and gastrointestinal adverse events. Even if those side effects are mild and not clinically threatening in most cases, the psychological burden may weigh heavy on the affected patients and can even result in treatment termination. Due to their simple mode of administration, EGFR-TKI are being used increasingly in outpatient settings. This review presents specific assessment and handling guidelines for the most frequent side effects. By this point of time, several EGFR-TKI have been approved, and further drugs e. g. afatinib are in late stages of clinical trials. Afatinib is a member of the most recent generation of TKIs (irreversible TKIs) with a broader field of action (Erb family blocker) and the typical class side effects.

Gastrointestinal side effects such as diarrhea are frequent and occur in most cases during the first days of treatment. Management of diarrhea is recommended to be handled similar to chemotherapy-induced diarrhea based on loperamide and octreotide as presented in this review. Relief for stomatitis/mucositis can be provided with effective topical care and cooling. Rash and dermatitis warrant specific topical and/or oral antibiotics in combination with local care, depending on the severity. Fatigue is infrequent under afatinib, but, if present, should be taken seriously.

Schlüsselwörter

TKI - EGFR - Sicherheit - Verträglichkeit - Nebenwirkungen - Hautveränderungen - Durchfall

Key words

TKI - EGFR - safety - tolerability - side effects - cutaneous toxicity - diarrhea

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