Section of Hematology and Oncology, University of Chicago, 5841 South Maryland Avenue, MC 2115, Chicago, IL, 60637, USA.
Cancer Chemother Pharmacol. 2014 Jun;73(6):1227-39. doi: 10.1007/s00280-014-2459-z. Epub 2014 Apr 9.
Treatment options for patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) are limited. The purpose of this study was to assess the efficacy and safety of zalutumumab in platinum-refractory R/M SCCHN.
Patients with platinum-refractory R/M SCCHN were enrolled if they had performance status of 0-2, age ≥18 years and adequate organ function. Patients received weekly infusions of zalutumumab individually titrated to a grade 2 skin rash. Primary objective was overall survival (OS), and secondary objectives were efficacy and safety. A subgroup analysis of OS and progression-free survival (PFS) was conducted for various demographic, disease-related and molecular factors.
Ninety patients were enrolled. Twenty-three percent of patients had performance status (PS) 2 and 74 % had distant metastases. Median OS was 5.3 months (95 % CI [4.1, 7.1]), and median PFS was 2.1 months (95 % CI [2.0, 2.6]). Subgroup analysis by ECOG PS revealed median OS of 6.3 months for PS = 0-1 and 2.5 months for PS = 2. Objective response rate was 5.7 %, and disease control rate was 39.8 %. Grade 3-4 adverse events related to zalutumumab were observed in 19 % of patients and included skin rash (5 %), hypomagnesemia (4 %) and pneumonitis (1 %). The frequency of all-cause grade 3-4 AEs was 62 % and included infections (14 %), gastrointestinal disorders (12 %) and hypokalemia (6 %). Two deaths were deemed related to zalutumumab [ClinicalTrials.gov Identifier: NCT00542308].
Zalutumumab showed reasonable efficacy in platinum-refractory R/M SCCHN patients, and dose titration based on skin rash evaluation was feasible.
铂类耐药复发性或转移性头颈部鳞状细胞癌（R/M SCCHN）患者的治疗选择有限。本研究旨在评估 zalutumumab 在铂类耐药 R/M SCCHN 患者中的疗效和安全性。
如果患者体能状态（PS）为 0-2，年龄≥18 岁且器官功能充足，则入组铂类耐药 R/M SCCHN 患者。患者接受个体化滴定至 2 级皮疹的 zalutumumab 每周输注。主要终点为总生存期（OS），次要终点为疗效和安全性。对各种人口统计学、疾病相关和分子因素进行 OS 和无进展生存期（PFS）的亚组分析。
共入组 90 例患者。23%的患者 PS 为 2，74%的患者有远处转移。中位 OS 为 5.3 个月（95%CI[4.1,7.1]），中位 PFS 为 2.1 个月（95%CI[2.0,2.6]）。ECOG PS 亚组分析显示 PS=0-1 的中位 OS 为 6.3 个月，PS=2 的中位 OS 为 2.5 个月。客观缓解率为 5.7%，疾病控制率为 39.8%。与 zalutumumab 相关的 3-4 级不良事件发生率为 19%，包括皮疹（5%）、低镁血症（4%）和肺炎（1%）。所有原因的 3-4 级 AE 发生率为 62%，包括感染（14%）、胃肠道疾病（12%）和低钾血症（6%）。2 例死亡被认为与 zalutumumab 相关[临床试验.gov 标识符：NCT00542308]。
zalutumumab 在铂类耐药 R/M SCCHN 患者中显示出合理的疗效，并且基于皮疹评估的剂量滴定是可行的。
