Barr Paul M, Miller Thomas P, Friedberg Jonathan W, Peterson Derick R, Baran Andrea M, Herr Megan, Spier Catherine M, Cui Haiyan, Roe Denise J, Persky Daniel O, Casulo Carla, Littleton Jamie, Schwartz Mark, Puvvada Soham, Landowski Terry H, Rimsza Lisa M, Dorr Robert T, Fisher Richard I, Bernstein Steven H, Briehl Margaret M
University of Rochester, Wilmot Cancer Center, Rochester, NY;
University of Arizona Cancer Center, Tucson, AZ;
Blood. 2014 Aug 21;124(8):1259-65. doi: 10.1182/blood-2014-04-570044. Epub 2014 Jul 11.
Lymphoma cells are subject to higher levels of oxidative stress compared with their normal counterparts and may be vulnerable to manipulations of the cellular redox balance. We therefore designed a phase 2 study of imexon (Amplimexon/NSC-714597), a prooxidant molecule, in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Imexon was administered at 1000 mg/m(2) IV daily for 5 days in 21-day cycles. Gene expression analysis performed on pretreatment tumor specimens included 13 transcripts used to generate a redox signature score, previously demonstrated to correlate with lymphoma prognosis. Twenty-two patients were enrolled having follicular (n = 9), diffuse large B-cell (DLBCL) (n = 5), mantle cell (n = 3), transformed follicular (n = 2), small lymphocytic (n = 2), and Burkitt (n = 1) lymphoma. The most common grade 3/4 adverse events were anemia (14%) and neutropenia (9%). The overall response rate was 30%, including responses in follicular lymphoma (4 of 9) and DLBCL (2 of 5). Gene expression analyses revealed CD68 and the redox-related genes, GPX1 and SOD2, as well as a higher redox score to correlate with clinical responses. Therefore, pretreatment markers of oxidative stress may identify patients likely to respond to this therapeutic approach. This trial was registered at www.clinicaltrials.gov as #NCT01314014.
与正常细胞相比，淋巴瘤细胞承受着更高水平的氧化应激，可能易受细胞氧化还原平衡调控的影响。因此，我们设计了一项针对复发/难治性B细胞非霍奇金淋巴瘤（NHL）患者的imexon（Amplimexon/NSC - 714597，一种促氧化剂分子）的2期研究。imexon以1000 mg/m²静脉注射，每日一次，共5天，每21天为一个周期。对预处理肿瘤标本进行的基因表达分析包括13种转录本，用于生成氧化还原特征评分，先前已证明该评分与淋巴瘤预后相关。入组的22例患者患有滤泡性淋巴瘤（n = 9）、弥漫性大B细胞淋巴瘤（DLBCL）（n = 5）、套细胞淋巴瘤（n = 3）、转化型滤泡性淋巴瘤（n = 2）、小淋巴细胞淋巴瘤（n = 2）和伯基特淋巴瘤（n = 1）。最常见的3/4级不良事件是贫血（14%）和中性粒细胞减少（9%）。总缓解率为30%，包括滤泡性淋巴瘤（9例中的4例）和DLBCL（5例中的2例）的缓解。基因表达分析显示，CD68以及氧化还原相关基因GPX1和SOD2，还有更高的氧化还原评分与临床反应相关。因此，氧化应激的预处理标志物可能有助于识别可能对这种治疗方法有反应的患者。该试验已在www.clinicaltrials.gov上注册，编号为#NCT01314014。
