Bradstock Kenneth F, Link Emma, Collins Marnie, Di Iulio Juliana, Lewis Ian D, Schwarer Anthony, Enno Arno, Marlton Paula, Hahn Uwe, Szer Jeff, Cull Gavin, Seymour John F
Department of Haematology, Westmead Hospital, Sydney, NSW, Australia.
Br J Haematol. 2014 Dec;167(5):618-25. doi: 10.1111/bjh.13086. Epub 2014 Aug 21.
Gastrointestinal toxicity, including oral mucositis, is a frequent complication of intensive combination chemotherapy for acute myeloid leukaemia (AML) and contributes substantially to treatment-related mortality. We conducted a placebo-controlled randomized trial to evaluate the efficacy of palifermin (keratinocyte growth factor), given at 60 μg/kg per daily IV for 3 d before and after chemotherapy, for mucosal protection in adult patients with previously untreated AML receiving induction therapy with idarubicin, high-dose cytarabine and etoposide. Among 155 randomized patients, there was no statistically significant difference in the rate of grade 3 and 4 oral mucositis (primary study endpoint) between the two treatment arms (three in palifermin arm (4%), 8 in placebo arm (10%; P = 0·21); however, when considering the severity of oral mucositis (World Health Organization grade 0-4), there was evidence of reduced rates of higher grades of oral mucositis in the palifermin arm (P = 0·0007, test for trend). There was a statistically significantly lower rate of grades 3 and 4 gastrointestinal adverse events in the palifermin arm (21% vs. 44% in placebo arm; P = 0·003), mainly due to a reduction in severe diarrhoea (8% palifermin, 26% placebo; P = 0·01). Palifermin has activity as a mucosal protectant in AML patients receiving intensive chemotherapy. This trial is registered at ACTRN012605000095662.
胃肠道毒性，包括口腔黏膜炎，是急性髓系白血病（AML）强化联合化疗常见的并发症，并且在很大程度上导致了治疗相关死亡率。我们进行了一项安慰剂对照随机试验，以评估在化疗前后3天每天静脉注射60μg/kg的帕利夫明（角质形成细胞生长因子）对接受伊达比星、大剂量阿糖胞苷和依托泊苷诱导治疗的初治成年AML患者的黏膜保护作用。在155例随机分组的患者中，两个治疗组之间3级和4级口腔黏膜炎的发生率（主要研究终点）无统计学显著差异（帕利夫明组3例（4%），安慰剂组8例（10%）；P = 0.21）；然而，考虑口腔黏膜炎的严重程度（世界卫生组织0 - 4级）时，有证据表明帕利夫明组较高等级口腔黏膜炎的发生率降低（P = 0.0007，趋势检验）。帕利夫明组3级和4级胃肠道不良事件的发生率在统计学上显著较低（21%对安慰剂组的44%；P = 0.003），主要是由于严重腹泻的减少（帕利夫明组8%，安慰剂组26%；P = 0.01）。帕利夫明对接受强化化疗的AML患者具有黏膜保护活性。该试验在澳大利亚新西兰临床试验注册中心注册号为ACTRN012605000095662。
