Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial.
BACKGROUND
Pixantrone dimaleate (pixantrone)--a novel aza-anthracenedione--was synthesised to reduce anthracycline-related cardiotoxicity without compromising antitumour efficacy. We aimed to assess the efficacy and safety of pixantrone versus an investigator's choice of a single-agent therapy in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma.


METHODS
In this phase 3, multicentre, open-label, randomised trial at 66 hospitals in Europe, India, Russia, South America, the UK, and the USA, patients with histologically confirmed aggressive non-Hodgkin lymphoma who had relapsed after two or more previous chemotherapy regimens were randomly assigned (1:1) by an interactive voice response system to treatment with pixantrone dimaleate (85 mg/m(2) intravenously on days 1, 8, and 15 of a 28-day cycle, for up to six cycles) or to a comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide, mitoxantrone, or gemcitabine) given at prespecified standard doses and schedules. Patients were stratified by region, International Prognostic Index score, and previous stem-cell transplantation. Patients and investigators were not masked to treatment assignment; however, an independent assessment panel was masked. The primary endpoint was the proportion of patients with a complete or unconfirmed complete response in the intention-to-treat (ITT) population at the end of treatment. Primary analyses of efficacy were based on the independent assessment panel's data review. The study is registered at ClinicalTrials.gov, number NCT00088530.


RESULTS
The ITT population comprised 70 patients randomly assigned to the pixantrone group and 70 to the comparator. Five patients (two in the pixantrone group and three in the comparator group) dropped out before receiving their study drug. 14 patients (20·0% [95% CI 11·4-31·3]) who received pixantrone achieved a complete or unconfirmed complete response at end of treatment compared with four patients (5·7% [1·6-14·0]) in the comparator group (p = 0·021). The most common grade 3 or 4 adverse events in patients given pixantrone were uncomplicated, non-cumulative neutropenia (28 [41·2%] of 68 patients vs 13 [19·4%] of 67 patients in the comparator group), leucopenia (16 [23·5%] vs five [7·5%]), and thrombocytopenia (eight [11·8%] vs seven [10·4%]).


CONCLUSIONS
Pixantrone, given as a single-agent salvage therapy in heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma, is efficacious and tolerable. It could be a treatment option for patients whose aggressive non-Hodgkin lymphoma has failed to respond to at least two previous chemotherapy regimens.


BACKGROUND
Cell Therapeutics, Inc.
St George's Hospital, London, UK. rpetteng@sgul.ac.uk
Ruth
R
Pettengell
Bertrand
B
Coiffier
Geetha
G
Narayanan
Fernando Hurtado
FH
de Mendoza
Raghunadharao
R
Digumarti
Henry
H
Gomez
Pier Luigi
PL
Zinzani
Gary
G
Schiller
David
D
Rizzieri
Giles
G
Boland
Paul
P
Cernohous
Lixia
L
Wang
Christine
C
Kuepfer
Igor
I
Gorbatchevsky
Jack W
JW
Singer
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy; D016277:Ventricular Function, Left / Q000187:drug effects
D000970:Antineoplastic Agents; D007546:Isoquinolines; C086548:pixantrone