Sequential vs Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer: Randomized Phase III Trial RTOG 9410
Sequential vs Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer: Randomized Phase III Trial RTOG 9410
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DOI：
10.1093/jnci/djr325
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发表时间：
2011-10-01
期刊：
影响因子：
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通讯作者：
Cox, James D.
中科院分区：
文献类型：
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作者：
Curran, Walter J., Jr.;Paulus, Rebecca;Cox, James D.
背景 与单独 TRT 相比，化疗联合胸部放疗 (TRT) 已被证明可以为 III 期非小细胞肺癌患者带来良好的体能状态患者的生存优势。然而，尚不清楚这些疗法的序贯还是同时给药是否是最佳组合策略。方法在一项三组 III 期试验中，总共 610 名患者被随机分配至两种并行方案和一种序贯化疗和 TRT 方案。序贯组包括在第 1 天和第 29 天使用 100 mg/m(2) 的顺铂，以及每周 5 mg/m(2) 的长春花碱，持续 5 周，并从第 50 天开始进行 60 Gy TRT。第 2 组使用与第 1 组相同的化疗方案，从第 1 天开始每天一次 60 Gy TRT。第 3 组在第 1、8 天使用 50 mg/m(2) 的顺铂， 29 号和 36 号患者分别在第 1、2、5 和 6 天口服依托泊苷 50 mg，每天两次，持续 10 周，从第 1 天开始以 1.2 Gy 每天两次的剂量提供 69.6 Gy。主要终点是总生存期，次要终点包括肿瘤反应和肿瘤进展时间。 Kaplan-Meier 分析用于评估生存率，并使用 Wilcoxon 秩和检验检查毒性作用。所有统计检验均为双边。结果 第 1-3 组的中位生存时间分别为 14.6、17.0 和 15.6 个月。与序贯治疗相比，采用每日一次 TRT 的同步治疗方案治疗的患者的五年生存率在统计学上显着更高（5 年生存率：序贯治疗，第 1 组，10% [20 名患者]，95% 置信区间 [CI] = 7% 至 15%；同步治疗，第 2 组，16% [31 名患者]，95% CI = 11% 至 22%，P = 0.046；同步，第 3 组， 13% [22 名患者]，95% CI = 9% 至 18%）。中位随访时间为 11 年，同时治疗的急性 3-5 级非血液学毒性反应发生率高于序贯治疗，但晚期毒性反应相似。 结论 与序贯治疗相比，顺铂化疗与 TRT 同步治疗可带来长期生存获益。
Background The combination of chemotherapy with thoracic radiotherapy (TRT) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non-small cell lung cancer. However, it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy.Methods A total of 610 patients were randomly assigned to two concurrent regimens and one sequential chemotherapy and TRT regimen in a three-arm phase III trial. The sequential arm included cisplatin at 100 mg/m(2) on days 1 and 29 and vinblastine at 5 mg/m(2) per week for 5 weeks with 60 Gy TRT beginning on day 50. Arm 2 used the same chemotherapy regimen as arm 1 with 60 Gy TRT once daily beginning on day 1. Arm 3 used cisplatin at 50 mg/m(2) on days 1, 8, 29, and 36 with oral etoposide at 50 mg twice daily for 10 weeks on days 1, 2, 5, and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions beginning on day 1. The primary endpoint was overall survival, and secondary endpoints included tumor response and time to tumor progression. Kaplan-Meier analyses were used to assess survival, and toxic effects were examined using the Wilcoxon rank sum test. All statistical tests were two-sided.Results Median survival times were 14.6, 17.0, and 15.6 months for arms 1-3, respectively. Five-year survival was statistically significantly higher for patients treated with the concurrent regimen with once-daily TRT compared with the sequential treatment (5-year survival: sequential, arm 1, 10% [20 patients], 95% confidence interval [CI] = 7% to 15%; concurrent, arm 2, 16% [31 patients], 95% CI = 11% to 22%, P = .046; concurrent, arm 3, 13% [22 patients], 95% CI = 9% to 18%). With a median follow-up time of 11 years, the rates of acute grade 3-5 nonhematologic toxic effects were higher with concurrent than sequential therapy, but late toxic effects were similar.Conclusion Concurrent delivery of cisplatin-based chemotherapy with TRT confers a long-term survival benefit compared with the sequential delivery of these therapies.