Centre Hospitalier Régional Universitaire de Besançon, Université de Franche-Comté, EA 3181, France.
Eur J Cancer. 2013 Aug;49(12):2654-64. doi: 10.1016/j.ejca.2013.04.013. Epub 2013 Jun 1.
There will be a detectable increase in overall survival (OS) using preoperative (PRE) as opposed to perioperative (PERI) chemotherapy in resectable StageI-II non-small-cell lung cancer (NSCLC).
This multicenter, open-label, randomised trial with a 2×2 factorial design first compared two chemotherapy strategies (PRE versus PERI), then two chemotherapy regimens (gemcitabine-cisplatin [GP] versus paclitaxel-carboplatin [TC]). The PRE group received two preoperative cycles followed by two additional preoperative cycles, while the PERI group underwent two preoperative cycles followed by two postoperative cycles, the 3rd and 4th cycles being given only to responders in both cases.
A total of 528 patients were randomised, 267 of which were assigned to the PRE group and 261 to the PERI group. Three-year OS did not differ between the two groups (67.4% and 67.7%, respectively; hazard ratio (HR)=1.01 [0.79-1.30], p=0.92), nor did 3-year disease-free survival, response rates, toxicity, or postoperative mortality. Pathological complete response was observed in 22 (8.2%) and 16 patients (6.1%), respectively. Although quality of life did not differ significantly, chemotherapy compliance was significantly higher in the PRE group. The proportion of responders who received Cycles 3 and 4 was significantly higher in the PRE group (90.4% versus 75.2%, p=0.001). In responders, the dose intensity of Cycles 3 and 4 was higher in the PRE group than in the PERI group (mean relative dose intensity of 90.4% versus 82.6%, respectively; p=0.0007). There was no difference between GP and TC in 3-year OS (HR=0.97 [95% confidence interval (CI): 0.76-1.25], p=0.80) or response rates. However, the regimens' toxicity profiles differed.
This study failed to demonstrate any difference in survival between patients receiving preoperative and perioperative chemotherapy in early-stage NSCLC. The increase from two to four preoperative chemotherapy cycles did not increase the pathological response rate.
与围手术期化疗相比，可切除 I 期- II 期非小细胞肺癌（NSCLC）患者采用术前化疗（PRE）可检测到总生存期（OS）的提高。
本多中心、开放标签、随机试验采用 2×2 析因设计，首先比较了两种化疗策略（PRE 与 PERI），然后比较了两种化疗方案（吉西他滨-顺铂[GP]与紫杉醇-卡铂[TC]）。PRE 组接受两个术前周期，然后再进行两个额外的术前周期，而 PERI 组则接受两个术前周期，然后再进行两个术后周期，只有在两种情况下均为应答者的患者才接受第 3 个和第 4 个周期的治疗。
共随机分配了 528 例患者，其中 267 例被分配至 PRE 组，261 例被分配至 PERI 组。两组患者的 3 年 OS 无差异（分别为 67.4%和 67.7%；风险比（HR）=1.01[0.79-1.30]，p=0.92），3 年无病生存率、缓解率、毒性或术后死亡率也无差异。病理学完全缓解分别见于 22 例（8.2%）和 16 例患者（6.1%）。尽管生活质量无显著差异，但 PRE 组的化疗依从性显著更高。在 PRE 组中，接受周期 3 和 4 治疗的应答者比例显著更高（90.4%比 75.2%，p=0.001）。在应答者中，PRE 组的周期 3 和 4 的剂量强度高于 PERI 组（平均相对剂量强度分别为 90.4%和 82.6%；p=0.0007）。GP 和 TC 在 3 年 OS（HR=0.97[95%置信区间（CI）：0.76-1.25]，p=0.80）或缓解率方面均无差异。然而，两种方案的毒性特征不同。
本研究未能证明早期 NSCLC 患者接受术前和围手术期化疗在生存方面存在差异。从两个周期增加到四个周期的术前化疗并没有提高病理缓解率。
