St George's Hospital, London, UK.
Lancet Oncol. 2012 Jul;13(7):696-706. doi: 10.1016/S1470-2045(12)70212-7. Epub 2012 May 30.
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.
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.
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%]).
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.
Cell Therapeutics, Inc.
马来酸匹柔比星（pixantrone）——一种新型的氮杂蒽二酮——被合成以降低蒽环类药物相关的心脏毒性，同时不影响抗肿瘤疗效。我们旨在评估 pixantrone 与研究者选择的单药治疗在复发或难治性侵袭性非霍奇金淋巴瘤的大量预处理患者中的疗效和安全性。
在这项由欧洲、印度、俄罗斯、南美洲、英国和美国的 66 家医院进行的 3 期、多中心、开放标签、随机试验中，经组织学证实患有侵袭性非霍奇金淋巴瘤且在两次或两次以上先前化疗方案后复发的患者，通过交互式语音应答系统按 1:1 随机分配（1:1）接受 pixantrone 二甲酸盐（85mg/m2 静脉注射，第 1、8 和 15 天，每 28 天为一个周期，最多 6 个周期）或比较剂（长春瑞滨、奥沙利铂、异环磷酰胺、依托泊苷、米托蒽醌或吉西他滨）以预先指定的标准剂量和方案给药。患者按区域、国际预后指数评分和先前的干细胞移植进行分层。患者和研究者未对治疗分配进行盲法，但独立评估小组进行了盲法。主要终点是在治疗结束时意向治疗（ITT）人群中完全或未确认完全缓解的患者比例。疗效的主要分析基于独立评估小组的数据审查。该研究在 ClinicalTrials.gov 注册，编号为 NCT00088530。
ITT 人群包括 70 例随机分配至 pixantrone 组和 70 例至比较剂组的患者。有 5 例（2 例在 pixantrone 组，3 例在比较剂组）在接受研究药物前退出。14 例（20.0%[95%CI 11.4-31.3]）接受 pixantrone 的患者在治疗结束时达到完全或未确认完全缓解，而比较剂组有 4 例（5.7%[1.6-14.0]）（p=0.021）。接受 pixantrone 的患者最常见的 3 级或 4 级不良事件为非累积性中性粒细胞减少症（28 例[41.2%]的 68 例患者与比较剂组的 13 例[19.4%]患者）、白细胞减少症（16 例[23.5%]与 5 例[7.5%]）和血小板减少症（8 例[11.8%]与 7 例[10.4%]）。
在复发或难治性侵袭性非霍奇金淋巴瘤的大量预处理患者中，作为单一药物进行挽救治疗的马来酸匹柔比星是有效且耐受良好的。对于那些侵袭性非霍奇金淋巴瘤对至少两种先前的化疗方案无反应的患者，它可能是一种治疗选择。
细胞治疗学公司。
