Lessons learned: Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%).
Background: Cabazitaxel is a second-generation taxane that improves the survival of patients with metastatic castrate-resistant prostate cancer following docetaxel therapy. Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. In this randomized phase II trial, we investigated cabazitaxel in patients with recurrent SCCHN.
Methods: Patients with incurable SCCHN with progression after platinum-based therapy were randomly assigned to cabazitaxel every 3 weeks (cycle 1, 20 mg/m2, increased to 25 mg/m2 for subsequent cycles in the absence of nonhematological adverse events [AEs] greater than grade 2 and hematological AEs greater than grade 3) or methotrexate (40 mg/m2/week). The patients were stratified according to their performance status and previous platinum-based chemotherapy for palliation versus curative intent. The primary endpoint was the progression-free survival rate (PFSR) at 18 weeks.
Results: Of the 101 patients, 53 and 48, with a median age of 58.0 years (range, 41-80), were randomly assigned to cabazitaxel or methotrexate, respectively. The PFSR at 18 weeks was 13.2% (95% confidence interval [CI], 5%-25%) for cabazitaxel and 8.3% (95% CI, 2%-20%) for methotrexate. The median progression-free survival was 1.9 months in both arms. The median overall survival was 5.0 and 3.6 months for cabazitaxel and methotrexate, respectively. More patients experienced serious adverse events with cabazitaxel than with methotrexate (54% vs. 36%). The most common drug-related grade 3-4 AE in the cabazitaxel arm was febrile neutropenia (17.3%).
Conclusion: This study did not meet its primary endpoint. Cabazitaxel has low activity in recurrent SCCHN.
试验信息
• ClinicalTrials.gov 注册号: NCT01528163
• 赞助: Cliniques Universitaires Saint-Luc
• 主要研究人: Jean-Pascal Henry Machiels
• IRB批准: 是
经验
• 卡巴他赛对头颈鳞癌 (SCCHN) 和紫杉烷类耐药细胞系具有活性。本研究首次对卡巴他赛在不能治愈的复发性SCCHN患者中进行调查。患者随机接受卡巴他赛每3周一次或甲氨蝶呤每周1次治疗。
• 本项II期研究未达到主要终点。
• 卡巴他赛在SCCHN中活性很低。
• 研究观察到发热性中性粒细胞减少的发生率高达17%, 因此卡巴他赛在这一人群的毒性特征也不佳。
摘要
背景. 卡巴他赛是第二代紫杉烷类, 用于曾接受多西他赛治疗的转移性去势抵抗性前列腺癌患者可改善其生存。卡巴他赛对头颈鳞癌 (SCCHN) 和紫杉烷类耐药细胞系具有活性。本研究为随机II期临床试验, 在复发性SCCHN患者中对卡巴他赛进行调查。
方法. 将接受含铂方案治疗后发生进展的不可治愈的SCCHN患者随机分配至卡巴他赛每3周一次[第1周期20 mg/m2, 后续周期如未发生>2级非血液学不良事件 (AE) 和>3级血液学AE则上调至25 mg/m2], 或甲氨蝶呤 (40 mg/m2/周) 组接受治疗。根据体能状态和既往含铂化疗为姑息性或治愈性目的对患者进行分层。主要终点为18周无进展生存率 (PFSR) 。
结果. 共纳入101例患者, 中位年龄58.0岁 (范围: 41∼80) , 53例随机分配至卡巴他赛组, 48例分配至甲氨蝶呤组。卡巴他赛组18周PFSR为13.2% [95%置信区间 (CI) : 5%∼25%], 甲氨蝶呤组为8.3% (95%CI: 2%∼20%) 。两组的中位无进展生存均为1.9个月。卡巴他赛组中位总生存为5.0个月, 甲氨蝶呤组为3.6个月。卡巴他赛组患者严重不良事件发生率高于甲氨蝶呤组 (54% vs. 36%) 。卡巴他赛组最常见的3∼4级药物相关性AE为发热性中性粒细胞减少 (17.3%) 。
结论. 本研究未达到主要终点。卡巴他赛在复发性SCCHN中活性较低。The Oncologist 2016;21:1416–1417
Trial registration: ClinicalTrials.gov NCT01528163.
©AlphaMed Press; the data published online to support this summary is the property of the authors.