Pixantrone: a novel aza-anthracenedione in the treatment of non-Hodgkin's lymphomas

Abstract

Pixantrone (BBR-2778) is a novel mitoxantrone-like drug, which lacks the 5,8-dihyroxy substitution groups thought to be responsible for the cardiac toxicity associated with mitoxantrone. In Phase I/II single-agent pixantrone clinical trials, neutropenia was the dose-limiting toxicity and the maximum tolerated dose was 150 mg/m²/week for 3 weeks every 4 weeks. In relapsed aggressive non-Hodgkin's lymphomas, weekly single-agent pixantrone 85 mg/m² for 3 weeks every 4 weeks was associated with a 27% overall response and a 15% complete response. When intensively pretreated patients with relapsed aggressive non-Hodgkin's lymphoma were treated with a cyclophosphamide, pixantrone, vincristine and prednisolone regimen (pixantrone substituted for doxorubicin in standard regimen [cyclophosphamide, doxorubicin, vincristine and prednisolone regimen (CHOP)]), the overall response was 74% and complete response 57%. In the BBR-2778, methylprednisolone, cisplatin and cytosine arabinoside (BSHAP) regimen, 58% overall response and 37% complete response were achieved. A number of randomised studies of pixantrone (BBR-2778) in patients with relapsed indolent or aggressive lymphomas are ongoing.

Keywords::

• cardiotoxicity
• pixantrone
• relapsed lymphoma