Medical Oncology Department, Grand Hospital of East Francilien-Marne-la-Vallée, Jossigny, France.
UMR_S1165, Inserm, University of Paris-Diderot, Paris, France.
Cancer Med. 2019 May;8(5):2005-2012. doi: 10.1002/cam4.2062. Epub 2019 Mar 10.
Docetaxel is a major anticancer drug that can induce hypersensitivity reactions leading to deleterious treatment interruptions. Blood hypereosinophilia could be a biological sign, potentially lethal, of delayed visceral hypersensitivity reactions. We hypothesized this biological event is probably underreported. In this prospective observational study, we followed up 149 patients treated with docetaxel monotherapy for breast or lung cancer. For each patient, blood eosinophil counts were recorded during docetaxel treatment and up to 3 months after the end of docetaxel treatment. For all patients, blood eosinophil counts significantly increased under docetaxel chemotherapy (P < 0.01). Seven percent had persistent eosinophilia after the end of treatment. Four patients had blood eosinophil counts over 1000/mm with severe cardiac, cutaneous and digestive toxicities, and docetaxel imputability was confirmed using drug-imputability scales. For two of these four patients, tissue biopsies were performed during the time of hypereosinophilia and of severe toxicities. Specific immunostainings and electron microscopy found numerous degranulating mast cells and eosinophils. Our study demonstrated that eosinophilia is frequent under docetaxel and could lead to severe complications, implicating eosinophils and mast cells, and possibly IgE. One way of treating hypersensitivity reactions could be by targeting IgEs with omalizumab, an anti-IgE monoclonal antibody approved for the treatment of severe allergic asthma, and successfully used in food and poison-induced anaphylactic reactions.
多西他赛是一种主要的抗癌药物,可引起过敏反应,导致治疗中断。血液嗜酸性粒细胞增多可能是迟发性内脏过敏反应的潜在致命的生物学标志。我们假设这种生物学事件可能报告不足。在这项前瞻性观察研究中,我们随访了 149 名接受多西他赛单药治疗的乳腺癌或肺癌患者。对于每位患者,在多西他赛治疗期间和多西他赛治疗结束后 3 个月内记录了血液嗜酸性粒细胞计数。所有患者的血液嗜酸性粒细胞计数在多西他赛化疗期间明显增加(P<0.01)。治疗结束后,有 7%的患者出现持续性嗜酸性粒细胞增多。有 4 名患者的血液嗜酸性粒细胞计数超过 1000/mm,伴有严重的心脏、皮肤和消化道毒性,使用药物归因量表确认了多西他赛的归因性。对于这 4 名患者中的 2 名,在嗜酸性粒细胞增多和严重毒性期间进行了组织活检。特异性免疫染色和电子显微镜发现了大量脱颗粒的肥大细胞和嗜酸性粒细胞。我们的研究表明,多西他赛治疗期间嗜酸性粒细胞增多很常见,可能导致严重并发症,涉及嗜酸性粒细胞和肥大细胞,可能还涉及 IgE。一种治疗过敏反应的方法可能是通过奥马珠单抗靶向 IgE,奥马珠单抗是一种抗 IgE 单克隆抗体,已被批准用于治疗严重过敏性哮喘,并成功用于食物和毒物引起的过敏反应。