From the University of TorontoToronto, and London Regional Cancer Centre, London, Ontario, Canada; Regional Hospital of Lung Disease and Tuberculosis, Poznan, Poland; Helsinki University, Helsinki, Finland; Alton Ochsner Medical Foundation, New Orleans, LA; Greenville Memorial Medical Center, Greenville, SC; University Hospitals of Cleveland, Cleveland, OH; Veterans Affairs Medical Center, Houston, TX; and Rhône-Poulenc Rorer, Collegeville, PA, and Paris, France.
J Clin Oncol. 2023 May 20;41(15):2673-2681. doi: 10.1200/JCO.22.02545.
To evaluate whether treatment with single-agent docetaxel would result in longer survival than would best supportive care in patients with non-small-cell lung cancer who had previously been treated with platinum-based chemotherapy. Secondary end points included assessment of response (docetaxel arm only), toxicity, and quality of life.
PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions were eligible for entry onto the study if they had undergone one or more platinum-based chemotherapy regimens and if they had adequate hematology and biochemistry parameters. They were excluded if they had symptomatic brain metastases or if they had previously been treated with paclitaxel. Patients were stratified by performance status and best response to cisplatin chemotherapy and were then randomized to treatment with docetaxel 100 mg/m (49 patients) or 75 mg/m (55 patients) or best supportive care. Patients in both arms were assessed every 3 weeks.
One hundred four patients (103 of whom were eligible for entry onto the study) were well balanced for prognostic factors. Of 84 patients with measurable lesions, six (7.1%) achieved partial responses (three patients at each dose level). Time to progression was longer for docetaxel patients than for best supportive care patients (10.6 6.7 weeks, respectively; < .001), as was median survival (7.0 4.6 months; log-rank test, = .047). The difference was more significant for docetaxel 75 mg/m patients, compared with corresponding best supportive care patients (7.5 4.6 months; log-rank test, = .010; 1-year survival, 37% 11%; χ test, = .003). Febrile neutropenia occurred in 11 patients treated with docetaxel 100 mg/m, three of whom died, and in one patient treated with docetaxel 75 mg/m. Grade 3 or 4 nonhematologic toxicity, with the exception of diarrhea, occurred at a similar rate in both the docetaxel and best supportive care groups.
Treatment with docetaxel is associated with significant prolongation of survival, and at a dose of 75 mg/m, the benefits of docetaxel therapy outweigh the risks.
评估单药多西紫杉醇治疗与最佳支持治疗相比，能否延长先前接受过铂类化疗的非小细胞肺癌患者的总生存期。次要终点包括评估反应（仅多西紫杉醇组）、毒性和生活质量。
纳入标准为体力状态（PS）0~2 分，Ⅲ B/Ⅳ期非小细胞肺癌，可测量或可评价病灶，接受过 1 种或多种铂类化疗方案且血液学和生化参数足够。有症状脑转移或先前接受过紫杉醇治疗的患者排除在外。根据 PS 和顺铂化疗的最佳反应进行分层，然后将患者随机分为多西紫杉醇 100 mg/m 组（49 例）、75 mg/m 组（55 例）或最佳支持治疗组。两组患者每 3 周进行评估。
104 例患者（其中 103 例符合入组条件）在预后因素方面具有良好的均衡性。84 例可测量病灶患者中，6 例（7.1%）获得部分缓解（两个剂量组各 3 例）。多西紫杉醇组患者的无进展生存期长于最佳支持治疗组（分别为 10.6 周和 6.7 周；<.001），中位生存期也长于最佳支持治疗组（分别为 7.0 周和 4.6 周；log-rank 检验，=.047）。多西紫杉醇 75 mg/m 组与相应的最佳支持治疗组相比，差异更显著（7.5 周和 4.6 周；log-rank 检验，=.010；1 年生存率分别为 37%和 11%；χ 检验，=.003）。多西紫杉醇 100 mg/m 组有 11 例患者出现发热性中性粒细胞减少症，其中 3 例死亡，75 mg/m 组有 1 例患者出现此症。两组的 3 级或 4 级非血液学毒性发生率除腹泻外，相似。
多西紫杉醇治疗可显著延长生存时间，且 75 mg/m 剂量的多西紫杉醇治疗的获益大于风险。
