Department of Sarcoma Medical Oncology, Section of Cytokines and Supportive Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Cell Mol Med. 2013 Nov;17(11):1371-84. doi: 10.1111/jcmm.12169. Epub 2013 Nov 19.
Mucositis is one of the most significant toxicities in cancer patients undergoing cytotoxic treatment. It can have a negative impact on both quality of life and health economics. Severe oral mucositis can contribute to hospitalization, need for narcotic analgesics, total parentral nutrition, suboptimal delivery of anti-neoplastic treatment, and morbidity and mortality. Palifermin, a recombinant derivative of human keratinocyte growth factor, is the first active agent approved by the FDA for the prevention of severe oral mucositis in patients undergoing haematopoietic stem cell transplantation (HSCT). Several studies have also shown significant reduction in the incidence, severity and/or duration of oral mucositis in other high-risk settings such as concurrent chemoradiotherapy (CT/RT) for patients with head and neck cancer, and use of mucotoxic chemotherapeutic agents such as doxorubicin in sarcoma and fluorouracil for the treatment of colorectal cancer. The reduction in mucositis has translated into amelioration of symptoms and improvement in daily functioning as measured by patient-reported outcome in multiple studies. The clinical response to palifermin appears to be related in part to epithelial proliferation and mucosal thickening. Palifermin also has other potential clinical applications including the acceleration of immune reconstitution and inhibition of graft-versus-host disease in patients undergoing HSCT, and mitigation of dysphagia in lung cancer patients treated with concurrent CT/RT. Palifermin is generally well tolerated with mild-to-moderate skin and oral adverse events. Future studies may expand the use of palifermin into other areas that would benefit from its cytoprotective and regenerative effects.
黏膜炎是接受细胞毒性治疗的癌症患者最主要的毒性反应之一。它会对生活质量和卫生经济学造成负面影响。严重的口腔黏膜炎会导致住院、需要使用麻醉性镇痛药、全胃肠外营养、抗肿瘤治疗效果不佳，以及发病率和死亡率增加。培洛昔芬（Palifermin）是一种人角质细胞生长因子的重组衍生物，是 FDA 批准的第一种用于预防造血干细胞移植（HSCT）患者严重口腔黏膜炎的活性药物。多项研究还表明，在其他高危环境中，如头颈部癌症的同步放化疗（CT/RT）和使用多柔比星（阿霉素）等黏液毒性化疗药物治疗肉瘤，以及氟尿嘧啶（5-FU）治疗结直肠癌，口腔黏膜炎的发生率、严重程度和/或持续时间显著降低。在多项研究中，黏膜炎的减少转化为症状的改善和日常生活功能的提高，这些都是通过患者报告的结果来衡量的。培洛昔芬的临床反应部分与上皮细胞增殖和黏膜增厚有关。培洛昔芬还有其他潜在的临床应用，包括加速 HSCT 患者的免疫重建和抑制移植物抗宿主病，以及减轻接受同步 CT/RT 的肺癌患者的吞咽困难。培洛昔芬一般具有良好的耐受性，皮肤和口腔的不良反应为轻至中度。未来的研究可能会将培洛昔芬的用途扩展到其他受益于其细胞保护和再生作用的领域。
