Department of Medicine, Division of Hematology/Oncology, Michael J. Crescenz VA Medical Center, Philadelphia, PA.
Department of Medicine, Division of Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
J Natl Cancer Inst. 2019 May 1;111(5):490-497. doi: 10.1093/jnci/djy133.
Concurrent chemoradiotherapy is an established component of the nonoperative management of locally advanced head and neck squamous cell carcinoma (HNSCC), but the standard dose of 100 mg/m2 cisplatin every 3 weeks is associated with clinically significant toxicity. Interest in a more tolerable regimen has led to the widespread use of weekly lower dose cisplatin, but few randomized trials have compared these approaches.
We examined outcomes of patients with stage III-IVb HNSCC treated with definitive intent chemoradiotherapy using either high-dose cisplatin (HDC) or low-dose cisplatin (LDC), using population-based Veterans Affairs data. In an intent-to-treat analysis, patients were assigned to the HDC vs LDC group according to the dose of their first cycle. Variables potentially influencing treatment decisions including cancer site, stage, smoking/alcohol use, and comorbidities were used to generate propensity scores (PS) for the use of HDC. We compared overall survival (OS) by treatment group using Cox regression, adjusting for PS. We then determined the risk of toxicities using PS-adjusted logistic regression.
A total of 2901 patients were included in the analysis; 2200 received HDC (mean initial dose 100 mg/m2). The mean initial dose of LDC was 40 mg/m2. After PS adjustment, HDC was not associated with improved OS over LDC (hazard ratio = 0.94, 95% confidence interval = 0.80 to 1.04). Adjusting for PS, HDC was associated with an increased risk of acute kidney injury, neutropenia, dehydration/electrolyte disturbance, and hearing loss.
In this large, population-based study of US military veterans, LDC was associated with similar survival to HDC in the nonoperative definitive management of locally advanced HNSCC of the oral cavity, oropharynx, and hypopharynx/larynx. HDC was associated with statistically significantly more toxicity than LDC. Adoption of LDC may reduce toxicity burden while maintaining OS.
同期放化疗是局部晚期头颈部鳞状细胞癌（HNSCC）非手术治疗的既定组成部分，但每 3 周 100mg/m2 顺铂的标准剂量与明显的临床毒性相关。对更耐受方案的兴趣导致每周低剂量顺铂的广泛使用，但很少有随机试验比较这些方法。
我们使用基于人群的退伍军人事务部数据，检查了接受根治性放化疗的 III-IVb 期 HNSCC 患者的治疗结果，这些患者使用高剂量顺铂（HDC）或低剂量顺铂（LDC）。在意向治疗分析中，根据患者第一周期的剂量将患者分配到 HDC 与 LDC 组。使用癌症部位、分期、吸烟/饮酒和合并症等潜在影响治疗决策的变量来生成 HDC 使用的倾向评分（PS）。我们使用 Cox 回归比较了治疗组的总生存率（OS），并调整了 PS。然后，我们使用 PS 调整的逻辑回归确定了毒性的风险。
共纳入 2901 例患者进行分析；2200 例患者接受 HDC（平均初始剂量 100mg/m2）。LDC 的平均初始剂量为 40mg/m2。经过 PS 调整后，HDC 与 LDC 相比并未改善 OS（风险比=0.94，95%置信区间=0.80 至 1.04）。调整 PS 后，HDC 与急性肾损伤、中性粒细胞减少症、脱水/电解质紊乱和听力损失的风险增加相关。
在这项针对美国退伍军人的大型基于人群的研究中，LDC 在口腔、口咽和下咽/喉的局部晚期 HNSCC 的非手术确定性治疗中与 HDC 的生存相似。HDC 与 LDC 相比，毒性明显更大。采用 LDC 可能会降低毒性负担，同时保持 OS。
