Arsentrioxid: „ein erfolgreiches Gift” bei Patienten mit akuter Promyelozytenleukämie

Zusammenfassung

Die Wirksamkeit von Arsenderivaten bei Neoplasien beruht auf komplexen Mechanismen. Bei der Therapie der akuten Promyelozytenleukämie (APL) steht ein dualer, zur Differenzierung und Apoptose der Blasten führender Effekt im Vordergrund.

Diese Zusammenfassung gibt einen Überblick über Aspekte der Pharmakologie, klinische Effizienz und unerwünschte Effekte von Arsentrioxid (ATO) bei APL. In 17 internationalen Studien zur Primär- und Rezidivtherapie mit ATO wurden insgesamt 565 Patienten eingeschlossen. Von den Patienten mit rezidivierter APL (n = 266) erreichten insgesamt 85,7 % eine Remission bei guter Verträglichkeit von ATO. Das Überleben nach 2 Jahren lag bei 50 bis 77 %. Bei neu diagnostizierter APL (n = 299) wurden Remissionsraten zwischen 73 und 95 % erreicht. Blutungskomplikationen, überwiegend zerebral, umfassten 66 % der Frühtodesfälle und waren die häufigste Todesursache. Die häufigste unerwünschte Begleiterscheinung von ATO war das APL-Differenzierungssyndrom bei bis zu 25 % der Patienten. Bei kurzen Beobachtungszeiten sind Langzeiteffekte noch nicht einschätzbar.

ATO erweist sich als hocheffizient in der Behandlung der APL. Es ist für die rezidivierte und refraktäre APL zugelassen.

Summary

he mechanism of action of arsenic derivates in neoplasitic disease is complex. Cell differentiation and apoptosis are of utmost importance in the therapy of acute promyelocytic leukemia (APL). This review considers essential aspects of the pharmacology, clinical efficacy and adverse effects of arsenic trioxide (ATO) in APL. So far ATO treatment has been investigated in 17 international studies encompassing 565 patients with either initially diagnosed or relapsed APL. 85.7% of patients with relapsed APL (n=266) had a remission and ATO was well tolerated. The overall survival after two years ranged from 50 to 77%. In the initial therapy of APL (n=299), complete remission was achieved in 73 to 95% of patients. The most frequent cause of death (66% of early deaths) was bleeding complications, mostly cerebral bleedings. The most common adverse effect of ATO (in up to 25% of patients) was the APL-differentiation syndrome. Because of the short follow-up periods, long-term effects cannot as yet be evaluated. Arsenic trioxide (ATO) is highly efficacious in the treatment of APL. Its use has been approved for relapsed and refractory APL.

Schlüsselwörter

Arsentrioxid - Promyelozytenleukämie

Key words

arsenic toxide - promyelocytic leukemia

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