Der Onkologe

, Volume 14, Issue 9, pp 940–950

Arzneistoffprofil: Nilotinib

Präklinik – Pharmakologie – Klinische Wirksamkeit – Toxizitäten
Update Onkologie
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Zusammenfassung

Nilotinib (AMN107) ist ein neuer, hoch selektiver and potenter Aminopyrimidin-Inhibitor der BCR-ABL-Tyrosinkinase, welcher in vitro um den Faktor 30 potenter als Imatinib ist. Nilotinib ist gegen 32 der 33 Mutationen wirksam, die zu einer Imatinib-Resistenz führen, mit Ausnahme der T315I-Mutation. Zusätzliche Aktivität besteht gegenüber KIT (c-KIT) sowie dem „platelet-derived growth factor receptor“ (PDGFR). Als Ergebnis dieser Eigenschaft, Tyrosinkinasen zielgerichtet zu hemmen, wurde Nilotinib bei der chronischen myeloischen Leukämie (CML), bei der Philadelphia-Chromosom-positiven akuten lymphatischen Leukämie (Ph+ALL) und anderen hämatologischen Malignomen (wie bei der systemischen Mastozytose und der chronischen eosinophilen Leukämie CEL) geprüft. Die präklinischen und klinischen Daten von Nilotinib demonstrieren dabei eine hohe Wirksamkeit gegen Imatinib-resistente, klinisch problematische Tyrosinkinase-Mutationen. Aufgrund dieser verbesserten pharmakologischen Eigenschaften wurde ein umfassendes klinisches Entwicklungsprogramm durchgeführt, welches zur Zulassung von Nilotinib in der Schweiz, den USA und in der EU im Jahre 2007 führte. Klinische Studien mit Nilotinib weisen ferner auf eine Aktivität gegen gastrointestinale Stromatumoren (GIST) hin.

Schlüsselwörter

Chronische myeloische Leukämie Nilotinib Medikamentöse Zweitlinientherapie Klinische Wirksamkeit Verträglichkeit 

Medication profile: nilotinib

Preclinical data – pharmacology – clinical effectiveness – toxicities

Abstract

Nilotinib (AMN107) is a novel highly selective and potent aminopyrimidine inhibitor of BCR-ABL tyrosine kinase that in vitro is 30 times more potent than imatinib. Nilotinib was designed to be a highly specific inhibitor of BCR-ABL with greater potency than imatinib. Nilotinib is active against 32/33 imatinib-resistant BCR-ABL mutations Additional activity was demonstrated against KIT (c-KIT) as well as against platelet-derived growth factor receptor. In animal models of leukemia, nilotinib has been shown to prevent and delay development of chronic myelogenous leukemia and improve survival. Nilotinib has demonstrated favorable efficacy and tolerability in phase I/II and phase II trials of patients with imatinib-resistant and imatinib-intolerant Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia. Nilotinib is well tolerated, as evidenced by its safety profile and high dose intensity.

Keywords

Chronic myelogenous leukemia Nilotinib Second-line Outcome Tolerability 

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Copyright information

© Springer Medizin Verlag 2008

Authors and Affiliations

  1. 1.Medizinische Klinik m.S. Hämatologie und OnkologieCampus Virchow Klinikum, Charité Universitätsmedizin BerlinBerlinDeutschland
  2. 2.Glashütten (früher: Med. Hochschule Hannover, Zentrum für Pharmakologie)HannoverDeutschland

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