Palifermin Decreases Severe Oral Mucositis of Patients Undergoing Postoperative Radiochemotherapy for Head and Neck Cancer: A Randomized, Placebo-Controlled Trial
Palifermin Decreases Severe Oral Mucositis of Patients Undergoing Postoperative Radiochemotherapy for Head and Neck Cancer: A Randomized, Placebo-Controlled Trial
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DOI：
10.1200/jco.2010.32.4103
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发表时间：
2011-07-10
影响因子：
45.3
通讯作者：
Berger, Dietmar
中科院分区：
文献类型：
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作者：
Henke, Michael;Alfonsi, Marc;Berger, Dietmar
目的头颈部肿瘤的放射化疗在大多数患者中会引起严重的粘膜炎。我们调查了帕利福明是否能减少这种衰弱的后遗症。方法我们对186例口腔、口咽、下咽或喉癌II至IVB期患者进行了一项多中心、双盲、随机、安慰剂对照试验。完全切除(R0)和不完全切除(R1)后分别给予60或66Gy2次/次和5次/周。顺铂100 mg/m(2)在第1天和第22天(与R1一起在第43天)给药。患者被随机分配，从前3天开始每周接受帕利福明120微克/公斤或安慰剂治疗，并一直持续到放化疗期间。训练有素的评估员每周进行两次口头评估。主要终点是严重口腔粘膜炎的发生率(世卫组织3至4级)。总体存活率和局部区域进展时间也被评估。结果92例服用帕利福明的患者中有47例(51%)出现严重的口腔粘膜炎，94例服用安慰剂的患者中有63例(67%)出现严重的口腔粘膜炎(P=0.027)。Palifermin缩短了持续时间(中位数为4.5vs22.0天)，延长了出现严重黏膜炎的时间(中位数为45vs32天)。患者报告的口腔和喉咙疼痛评分和治疗中断在治疗组之间都没有不同。经过32.8个月的中位随访期，接受帕利福明和安慰剂治疗的患者中，两组均有23人死亡(25%)，疾病复发分别为25人(27%)和22人(24%)。结论帕利福明降低了接受术后放疗的头颈部癌症患者严重口腔粘膜炎的发生率。帕利福明联合术后放化疗的临床探索将是有用的。
PurposeRadiochemotherapy of head and neck cancer causes severe mucositis in most patients. We investigated whether palifermin reduces this debilitating sequela.MethodsWe conducted a multicenter, double-blind, randomized, placebo-controlled trial in 186 patients with stages II to IVB carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients received 60 or 66 Gy after complete (R0) or incomplete resection (R1), respectively, at 2 Gy/fraction and five fractions per week. Cisplatin 100 mg/m(2) was administered on days 1 and 22 (and on day 43 with R1). Patients were randomly assigned to receive weekly palifermin 120 mu g/kg or placebo from 3 days before and continuing throughout radiochemotherapy. Trained evaluators performed oral assessments twice weekly. The primary end point was the incidence of severe oral mucositis (WHO grades 3 to 4). Overall survival and time to locoregional progression were also assessed. Analysis was by intention to treat.ResultsSevere oral mucositis was seen in 47 (51%) of 92 patients administered palifermin and 63 (67%) of 94 administered placebo (P = .027). Palifermin decreased the duration (median, 4.5 v 22.0 days) and prolonged the time to develop (median, 45 v 32 days) severe mucositis. Neither patient-reported mouth and throat soreness scores nor treatment breaks differed between treatment arms. After median follow-up of 32.8 months, 23 deaths (25%) had occurred in both treatment arms, and disease had recurred in 25 (27%) and 22 (24%) of palifermin- and placebo-treated patients, respectively.ConclusionPalifermin reduced the occurrence of severe oral mucositis in patients with head and neck cancer undergoing postoperative radiochemotherapy. Additional clinical exploration of palifermin with postoperative radiochemotherapy would be useful.