University of California, San Francisco, Melanoma Program, San Francisco 1600 Divisadero St, Rm A741, Box 1770, San Francisco, CA 94115, USA.
Expert Opin Biol Ther. 2012 Aug;12(8):1087-99. doi: 10.1517/14712598.2012.694421. Epub 2012 Jun 14.
Both native IFNα2b and pegylated IFNα2b (PegIFNα2b) are approved for the adjuvant treatment of high-risk melanoma.
This review compares the toxicity profiles of high-dose IFNα2b (HDI) and PegIFNα2b, and provides recommendations on the management of common PegIFNα2b-related toxicities, based on available clinical data and published literature.
The toxicity profile of PegIFNα2b at the approved dose (6 μg/kg/week for 8 weeks then 3 μg/kg/week for up to 5 years) is qualitatively similar to HDI in melanoma. The most common adverse events (AEs) are fatigue, anorexia, hepatotoxicity, flu-like symptoms, injection site reactions and depression. However, fatigue and flu-like symptoms appear less severe with PegIFNα2b, and toxicity seems to occur earlier, whereas with HDI toxicity may increase with time. Most AEs can be managed effectively by dose modification and aggressive symptom control. Dosing to tolerance using a three-step dose reduction schedule to maintain an ECOG performance status of 0 - 1 may enable patients experiencing toxicity to remain on treatment; this can be applied readily in clinical practice. PegIFNα2b is therefore a valuable alternative option for adjuvant treatment in melanoma, with a toxicity profile similar to that of HDI overall but a more convenient administration schedule.
天然干扰素 α2b 和聚乙二醇化干扰素 α2b(PegIFNα2b)均被批准用于辅助治疗高危黑色素瘤。
本文比较了高剂量干扰素 α2b(HDI)和 PegIFNα2b 的毒性特征,并根据现有临床数据和已发表的文献,就 PegIFNα2b 相关常见毒性的管理提供建议。
在批准的剂量(8 周时 6μg/kg/周,然后 5 年时 3μg/kg/周)下,PegIFNα2b 的毒性特征与黑色素瘤中的 HDI 相似。最常见的不良反应(AE)是疲劳、厌食、肝毒性、流感样症状、注射部位反应和抑郁。然而,与 PegIFNα2b 相比,疲劳和流感样症状似乎不太严重,而且毒性似乎出现得更早,而在 HDI 中,毒性可能会随时间增加。大多数不良反应可以通过剂量调整和积极的症状控制来有效管理。使用三步剂量降低方案以耐受剂量进行治疗,以保持 ECOG 表现状态为 0-1,可使正在接受治疗的患者耐受毒性;这在临床实践中易于应用。因此,PegIFNα2b 是黑色素瘤辅助治疗的一种有价值的替代选择,其毒性特征与 HDI 总体相似,但给药方案更方便。