Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.
Lung Cancer. 2011 Sep;73(3):338-44. doi: 10.1016/j.lungcan.2011.01.001. Epub 2011 Feb 5.
The role of chemotherapy for advanced NSCLC patients and ECOG PS2 remains controversial. We evaluated 4 doses of 3-weekly docetaxel to identify a less toxic, clinically effective dose.
Seventy-three patients with stage III (22%) (unsuitable for radical surgery/radiotherapy) and IV (78%) NSCLC were randomized to receive 4 doses of 3-weekly docetaxel, for 4 cycles: arm (A) 40 mg/m(2) (n=17), arm (B) 50 mg/m(2) (n=17), arm (C) 60 mg/m(2) (n=19), arm (D) 50 mg/m(2) escalated by 10 mg/m(2) to a maximum of 70 mg/m(2) (n=19). Primary endpoints: maximum tolerated dose, RR, duration of response, symptom improvement, toxicity and QoL. Secondary endpoint: overall survival (OS). Patients and disease characteristics were well balanced. Median age was 67 (range 45-81), there were 32 male and 41 female, histology subtype: squamous/adenocarcinoma/mixed/NOS=42%/49%/4%/5%.
Seven patients did not receive any treatment because of deterioration in PS or death. 50% of patients in arm D, who received more than one cycle, received dose escalation. There was no statistical difference in the number of cycles administered (arms A, B and D: median 2 cycles and arm C: median 3 cycles) and no difference in RR: arm A=6%, arm B=6%, arm C=10%, and arm D=0%. There was no statistically significant difference in grade 3/4 neutropenia and thrombocytopenia between the four arms. No difference was observed in hospitalization rate, blood transfusions, antibiotics administration and non-haematological toxicity. QoL: no difference in total scores between baseline and cycles 1-4. There was a significant decrease in pain scores from baseline to post cycles 2 and 3 (p=0.025 and p=0.002, respectively). There was no difference in OS (p=0.992). Median survival and 6-month survival were 61, 86, 88 and 97 days and 29%, 33%, 21% and 26% for arms A, B, C, and D, respectively.
Clinical efficacy of docetaxel was observed at all dose levels. Higher dose levels were not associated with increased toxicities, use of IV antibiotics or hospitalization rates. However, the median survival observed is shorter than historical data and do not support further evaluation of these doses of single agent docetaxel in this population.
对于晚期 NSCLC 患者和 ECOG PS2，化疗的作用仍存在争议。我们评估了 4 个剂量的 3 周 docetaxel，以确定一种毒性更小、临床有效的剂量。
73 例 III 期（22%）（不适合根治性手术/放疗）和 IV 期（78%）NSCLC 患者被随机分为 4 组，接受 4 个周期的 3 周 docetaxel 治疗：A 组（n=17）为 40mg/m2，B 组（n=17）为 50mg/m2，C 组（n=19）为 60mg/m2，D 组（n=19）为 50mg/m2，递增 10mg/m2，最大剂量为 70mg/m2。主要终点：最大耐受剂量、RR、缓解持续时间、症状改善、毒性和 QoL。次要终点：总生存（OS）。患者和疾病特征均衡。中位年龄为 67 岁（范围 45-81），32 名男性和 41 名女性，组织学亚型：鳞癌/腺癌/混合/NOS=42%/49%/4%/5%。
由于 PS 恶化或死亡，7 名患者未接受任何治疗。D 组 50%的患者接受了超过 1 个周期的剂量递增。接受的治疗周期数（A 组、B 组和 D 组：中位数为 2 个周期，C 组：中位数为 3 个周期）和 RR 无统计学差异：A 组=6%，B 组=6%，C 组=10%，D 组=0%。4 组间 3/4 级中性粒细胞减少症和血小板减少症无统计学差异。住院率、输血、抗生素使用和非血液学毒性无差异。QoL：总评分在基线和第 1-4 周期之间无差异。疼痛评分从基线到第 2 和第 3 周期显著下降（p=0.025 和 p=0.002）。OS 无差异（p=0.992）。中位生存期和 6 个月生存率分别为 61、86、88 和 97 天，以及 29%、33%、21%和 26%，分别为 A、B、C 和 D 组。
在所有剂量水平均观察到 docetaxel 的临床疗效。更高的剂量水平与毒性增加、IV 抗生素使用或住院率增加无关。然而，观察到的中位生存期较短，与历史数据不一致，因此不支持进一步评估该人群中单药 docetaxel 的这些剂量。
