Zatloukal Petr, Petruzelka Lubos, Zemanova Milada, Havel Libor, Janku Filip, Judas Libor, Kubik Antonin, Krepela Evzen, Fiala Pavel, Pecen Ladislav
Department of Pneumology and Thoracic Surgery, 3rd Faculty of Medicine, Faculty Hospital Bulovka, Charles University, Budinova 2, 18081 Prague, Czech Republic.
Lung Cancer. 2004 Oct;46(1):87-98. doi: 10.1016/j.lungcan.2004.03.004.
The superiority of chemoradiotherapy (CRT) over radiation alone in locally advanced non-small cell lung cancer (NSCLC) has been proven, but the relative merits of a concurrent schedule versus their sequential administration are less clear. This study compared the safety and efficacy of concurrent and sequential CRT, with chemotherapy (CT) consisting of a cisplatin and vinorelbine regimen, in patients with locally advanced NSCLC.
One hundred and two previously untreated patients (aged 42-75 years) with locally advanced, stage IIIA (n = 15) or stage IIIB (n = 87) NSCLC were entered into the study. The CT schedule consisted of up to four cycles of cisplatin 80 mg/m(2) on day 1, and vinorelbine 25 mg/m(2) at the first and fourth cycles (12.5 mg/m(2) during the 2nd/3rd cycles) on days 1, 8, 15 of a 28-day cycle. Radiotherapy (RT) was prescribed at a dose of 60 Gy/30 fractions, given as five fractions per week for 6 weeks. In the concurrent arm (arm A), RT was started on day 4 of cycle 2; whilst in the sequential arm (arm B), RT started within 2 weeks after completion of CT. Fifty-two patients were randomized to concurrent treatment and 50 to the sequential schedule.
Overall survival was significantly longer in arm A (median survival 16.6 months) versus arm B (median survival 12.9 months) (P = 0.023 by means of log-rank test; hazard ratio HR = 0.61, 95% CI of HR (0.39-0.93)), and time to progression (TTP) was also significantly longer in arm A (median time to progression 11.9 months) versus arm B (median time to progression 8.5 months) (P = 0.024 by means of log-rank test; HR = 0.62, 95% CI of HR (0.38-0.93)). Ninety-eight patients were evaluable for response and 101 for toxicity. The overall response rate was significantly higher in arm A, 80% (with 21% complete response (CR)) compared with 47% (with 17% CR) in arm B (P = 0.001 by means of chi(2)-test). WHO grade 3 or 4 toxicity was more frequent in arm A than in arm B, with a significantly greater incidence of leucopenia (53% versus 19%, P = 0.009 by means of chi(2) test) and nausea/vomiting (39% versus 15%, P = 0.044 by means of chi(2) test). There were no treatment related deaths.
In this study population, concurrent CRT demonstrated significant benefit in terms of response rate, overall survival and time to progression over sequential CRT. The concurrent CRT schedule was associated with higher toxicity; however, the adverse event profile was acceptable in both arms.
已证实放化疗（CRT）在局部晚期非小细胞肺癌（NSCLC）中优于单纯放疗，但同步方案与序贯方案的相对优势尚不清楚。本研究比较了同步和序贯CRT联合顺铂和长春瑞滨方案化疗（CT）在局部晚期NSCLC患者中的安全性和疗效。
102例既往未接受过治疗的局部晚期IIIA期（n = 15）或IIIB期（n = 87）NSCLC患者（年龄42 - 75岁）纳入本研究。CT方案为在第1天给予顺铂80 mg/m²，共4个周期，长春瑞滨在第1、4周期为25 mg/m²（第2/3周期为12.5 mg/m²），于28天周期的第1、8、15天给药。放疗（RT）处方剂量为60 Gy/30次分割，每周5次，共6周。在同步组（A组），RT于第2周期第4天开始；而在序贯组（B组），RT在CT完成后2周内开始。52例患者随机接受同步治疗，50例接受序贯方案。
A组的总生存期显著长于B组（中位生存期16.6个月对12.9个月）（对数秩检验P = 0.023；风险比HR = 0.61，HR的95%CI为(0.39 - 0.93)），A组的疾病进展时间（TTP）也显著长于B组（中位疾病进展时间11.9个月对8.5个月）（对数秩检验P = 0.024；HR = 0.62，HR的95%CI为(0.38 - 0.93)）。98例患者可评估疗效，101例可评估毒性。A组的总缓解率显著高于B组，分别为80%（完全缓解（CR）率21%）和47%（CR率17%）（卡方检验P = 0.001）。WHO 3/4级毒性在A组比B组更常见，白细胞减少症（53%对19%，卡方检验P = 0.009）和恶心/呕吐（39%对15%，卡方检验P = 0.044）的发生率显著更高。无治疗相关死亡。
在本研究人群中，同步CRT在缓解率、总生存期和疾病进展时间方面显示出比序贯CRT有显著益处。同步CRT方案的毒性更高；然而，两组的不良事件情况均可接受。
