London Health Sciences Centre, London, Ontario, Canada; Department of Oncology, Western University, London, Ontario, Canada.
London Health Sciences Centre, London, Ontario, Canada; Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
Cancer Treat Rev. 2014 Oct;40(9):1073-9. doi: 10.1016/j.ctrv.2014.08.002. Epub 2014 Aug 27.
Cytotoxic chemotherapy remains a standard treatment option for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN), but its effectiveness is debatable. We hypothesized palliative chemotherapy efficacy has decreased due to intensification of primary treatment, and investigated this by examining time trends of objective response rates (ORRs) in published reports of randomized trials (RCTs).
RCTs with at least one arm studying chemotherapy alone in RMSCCHN patients and reporting ORR were identified and data extracted. Eligible regimens had at least 6 trial arms reporting ORR over 20 years. Weighted linear regressions of ORR by year of publication for eligible regimens were done, and predictors of ORR and survival were examined.
Three regimens were eligible for analysis: low dose methotrexate, single agent cisplatin, and cisplatin plus infusional 5-fluorouracil (PF). Linear regression showed decreasing ORRs over time for all three regimens studied: 23.5 to 9.8% (1980-2010) for methotrexate (p=0.06), 19.6 to 8.8% (1980-2010) for cisplatin (p=0.0013), and 37.6 to 27.9% (1990-2010) for PF (p=0.11). Trial sample size, oropharynx cancer primary site, use of PF, and prior treatment increased over time. Use of PF and year of publication were the strongest predictors of ORR.
These data confirm the limited effectiveness of currently available palliative chemotherapy regimens for RMSCCHN patients. Novel therapeutics offering improvements in quality and quantity of life are urgently needed for these patients. Based on these results, the study of such agents as first-line therapy in RMSCCHN patients is entirely justifiable.
细胞毒性化疗仍然是复发性或转移性头颈部鳞状细胞癌（RMSCCHN）患者的标准治疗选择，但疗效存在争议。我们假设由于主要治疗的强化，姑息性化疗的疗效已经下降，并通过检查已发表的随机试验（RCT）报告中的客观缓解率（ORR）的时间趋势来对此进行研究。
确定了至少有一个臂研究 RMSCCHN 患者单独化疗并报告 ORR 的 RCT，并提取了数据。合格的方案在 20 多年中至少有 6 个试验臂报告 ORR。对合格方案的发布年份进行 ORR 的加权线性回归，并检查 ORR 和生存的预测因素。
有 3 种方案符合分析要求：低剂量甲氨蝶呤、单药顺铂和顺铂加输注氟尿嘧啶（PF）。线性回归显示所有三种方案的 ORR 随时间呈下降趋势：甲氨蝶呤为 23.5 至 9.8%（1980-2010 年）（p=0.06），顺铂为 19.6 至 8.8%（1980-2010 年）（p=0.0013），PF 为 37.6 至 27.9%（1990-2010 年）（p=0.11）。试验样本量、口咽癌原发部位、PF 的使用以及先前的治疗随时间增加。PF 的使用和发布年份是 ORR 的最强预测因素。
这些数据证实了目前用于 RMSCCHN 患者的姑息性化疗方案的疗效有限。这些患者迫切需要提供生活质量和数量改善的新疗法。基于这些结果，对头颈部鳞状细胞癌患者进行一线治疗的此类药物的研究是完全合理的。
