First Clinical Experience with the Magnetic Resonance Imaging Contrast Agent and Superoxide Dismutase Mimetic Mangafodipir as an Adjunct in Cancer Chemotherapy-A Translational Study
First Clinical Experience with the Magnetic Resonance Imaging Contrast Agent and Superoxide Dismutase Mimetic Mangafodipir as an Adjunct in Cancer Chemotherapy-A Translational Study
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DOI：
10.1593/tlo.11277
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发表时间：
2012-02-01
影响因子：
5
通讯作者：
Falkmer, Ursula G.
中科院分区：
文献类型：
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作者：
Karlsson, Jan Olof G.;Adolfsson, Karin;Falkmer, Ursula G.
临床前研究表明，临床批准的磁共振成像造影剂mangafodipir可以防止化疗引起的不良事件（AE），而不会对抗癌疗效产生负面影响。目前的转化研究测试了在III期结肠癌（Dukes' C）中用mangafodipir预处理是否降低治愈性（辅助）FOLFOX 6化疗期间的AE。该研究最初计划纳入20名患者，但由于未预见到mangafodipir从市场上撤出，该研究不得不在纳入14名患者后关闭。撤回mangafodipir完全是出于生产商的商业考虑，而不是出于任何安全问题。患者在12个计划周期的前3个周期接受治疗。患者随机接受5分钟的mangafodipir或安慰剂输注（每组7例）。根据美国国家癌症研究所（NCI）不良事件通用术语标准和赛诺菲-NCI标准评价AE。主要终点为中性粒细胞减少和感觉神经毒性。在安慰剂组的4名患者中有4例3级AE（严重）和1例4级AE（危及生命），而在曼戈地匹组中没有（P <0.05）。在3级和4级事件中，2例为中性粒细胞减少症，1例为感觉神经毒性。此外，FOLFOX治疗后，曼戈地匹组的白色血细胞计数在统计学上显著高于安慰剂组（P <0.01）。这项小型可行性研究似乎证实了临床前已证实的结果，即在结肠癌患者中，用mangafodipir预处理可降低辅助5-氟尿嘧啶加奥沙利铂化疗期间的AE。
Preclinical research suggests that the clinically approved magnetic resonance imaging contrast agent mangafodipir may protect against adverse events (AEs) caused by chemotherapy, without interfering negatively with the anticancer efficacy. The present translational study tested if pretreatment with mangafodipir lowers AEs during curative (adjuvant) FOLFOX6 chemotherapy in stage III colon cancer (Dukes' C). The study was originally scheduled to include 20 patients, but because of the unforeseen withdrawal of mangafodipir from the market, the study had to be closed after 14 patients had been included. The withdrawal of mangafodipir was purely based on commercial considerations from the producer and not on any safety concerns. The patients were treated throughout the first 3 of 12 scheduled cycles. Patients were randomized to a 5-minute infusion of either mangafodipir or placebo (7 in each group). AEs were evaluated according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events and the Sanofi-NCI criteria. The primary end points were neutropenia and neurosensory toxicity. There were four AEs of grade 3 (severe) and one AE of grade 4 (life threatening) in four patients in the placebo group, whereas there were none in the mangafodipir group (P < .05). Of the grade 3 and 4 events, two were neutropenia and one was neurosensory toxicity. Furthermore, white blood cell count was statistically, significantly higher in the mangafodipir group than in the placebo group (P < .01) after treatment with FOLFOX. This small feasibility study seems to confirm what has been demonstrated preclinically, namely, that pretreatment with mangafodipir lowers AEs during adjuvant 5-fluorouracil plus oxaliplatin-based chemotherapy in colon cancer patients.