Pixantrone in the treatment of non‑Hodgkin lymphoma

02/2017

MUDr. Juraj Ďuraš^{1, 2}, MUDr. Michal Kaščák¹, MUDr. Milan Navrátil¹, prof. MUDr. Roman Hájek, CSc.^{1, 2}

1. Klinika hematoonkologie FN Ostrava

2.Lékařská fakulta Ostravské univerzity, Ostrava

SUMMARY

Pixantrone is a novel aza-anthracenedione developed with aim of reducing cardiac toxicity whilst preserving the efficacy of anthracyclines. Pixantrone acts as an intercalating and an alkylating agent and weak topoisomerase II inhibitor. Unlike anthracycline pixantrone has reduced potential for the production of oxygen free radicals, which are probably the main factor of anthracycline’s cardiotoxicity. The maximum tolerated dose identified in the phase I study in relapsed and refractory aggressive non-Hodgkin’s lymphoma was 56 mg/m2 i.v. day 1, 8 and 15 in a 28day cycle. In Phase II and III was observed overall response in 27–40 %, complete remission in approximately 15 % of patients. In a randomized phase III study PIX 301 chieved overall response rate (40 %), complete or unconfirmed complete remission (24 %) and median time to progression (5,3 months) in the pixantrone arm was significantly higher than in the arm with single agent investigator choice. The main side effect of drug is haematotoxicity, primarily neutropenia. The risk of cardiotoxicity is not completely eliminated, but unlike in anthracyclines involves mainly subclinical decrease in left ventricular ejection fraction, symptomatic congestive hear failure has been observed only rarely. Based on the study PIX 301 pixantrone was approved in monotherapy in the treatment of multiple relapsed or refractory aggressive B-non-Hodgkin lymphomas. Efficacy of pixantrone combined with rituximab vs. gemcitabine + rituximab in rituximab pretreated patients is investigated in the ongoing PIX 306 study.

KEY WORDS

pixantrone, non-Hodgkin lymphoma, relapse, cardiotoxicity