Gebbia Vittorio, Gridelli Cesare, Verusio Claudio, Frontini Luciano, Aitini Enrico, Daniele Bruno, Gamucci Teresa, Mancuso Gianfranco, Di Maio Massimo, Gallo Ciro, Perrone Francesco, Morabito Alessandro
Università di Palermo, Casa di Cura La Maddalena, Palermo, Italy.
Lung Cancer. 2009 Feb;63(2):251-8. doi: 10.1016/j.lungcan.2008.05.027. Epub 2008 Jul 15.
Doublet chemotherapy is more effective than single-agent as first line treatment of advanced non-small-cell lung cancer (NSCLC). No reliable information instead is available on the effect of doublets in second line treatment. The aim of DISTAL-2 study was to compare two doublets containing docetaxel with single agent docetaxel as second line treatment of patients with NSCLC (ClinicalTrials.gov id.:.NCT00345059).
NSCLC patients, aged <75, PS 0-2, who had failed platinum-based chemotherapy, were randomly assigned with a 3:1:1 ratio to: arm A, weekly docetaxel (33.3mg/m(2) on days 1, 8, 15 q 4 weeks); arm B, weekly docetaxel (30 mg/m(2) on days 1, 8, 15) plus gemcitabine (800 mg/m(2) on days 1, 8 q 4 weeks) or plus vinorelbine (20mg/m(2) on days 1, 8 q 4 weeks) depending on which of the two had been used in first line; arm C, weekly docetaxel (as in arm B) plus capecitabine (625 mg/m(2) twice daily on days 5-18 q 4 weeks). Primary end-point was overall survival (OS). Two comparisons were planned: arm B vs. A and arm C vs. A. Overall, 375 patients had to be randomized. Response was assessed by RECIST, quality of life (QoL) by EORTC questionnaires.
84 patients were randomized from May 2005 to December 2006, when the trial was prematurely stopped due to the slow accrual. After 62 deaths, median OS was 40.0 weeks in arm A, 32.6 weeks in arm B (p=0.18 vs. A) and 39.7 weeks in arm C (p=0.90 vs. A). Response rate was 6.4, 16.7 and 5.3%, and median progression-free survival was 12.4, 13.1 and 11.9 weeks, for arms A, B and C, respectively. Patients in arm B had significantly more grade 3-4 haematological and non-haematological toxicity compared to arm A, and patients in arm C had significantly more grade 3-4 non-haematological toxicity compared to arm A. No relevant differences were found in QoL analysis, with the exception of significant worsening in appetite, vomiting and hemoptysis for patients in arm B.
Due to early termination, the trial does not have the planned statistical power. However, available data do not support the role of docetaxel-based combination chemotherapy as second line in advanced NSCLC.
在晚期非小细胞肺癌（NSCLC）的一线治疗中，双联化疗比单药化疗更有效。然而，关于双联化疗在二线治疗中的效果，尚无可靠信息。DISTAL-2研究的目的是比较两种含多西他赛的双联化疗方案与单药多西他赛作为NSCLC患者二线治疗的效果（ClinicalTrials.gov标识符：NCT00345059）。
年龄＜75岁、体能状态（PS）为0 - 2且铂类化疗失败的NSCLC患者，按3:1:1的比例随机分配至：A组，每周多西他赛（第1、8、15天，33.3mg/m²，每4周重复）；B组，每周多西他赛（第1、8、15天，30mg/m²）加吉西他滨（第1、8天，800mg/m²，每4周重复）或加长春瑞滨（第1、8天，20mg/m²，每4周重复），具体取决于一线使用的是两者中的哪一种；C组，每周多西他赛（同B组）加卡培他滨（第5 - 18天，625mg/m²，每日2次，每4周重复）。主要终点为总生存期（OS）。计划进行两项比较：B组与A组以及C组与A组。总体而言，需随机分配375例患者。采用实体瘤疗效评价标准（RECIST）评估疗效，通过欧洲癌症研究与治疗组织（EORTC）问卷评估生活质量（QoL）。
从2005年5月至2006年12月，共84例患者被随机分组，由于入组缓慢，试验提前终止。62例死亡后，A组的中位OS为40.0周，B组为32.6周（与A组相比，p = 0.18），C组为39.7周（与A组相比，p = 0.90）。A、B、C组的缓解率分别为6.4%、16.7%和5.3%，中位无进展生存期分别为12.4周、13.1周和11.9周。与A组相比，B组3 - 4级血液学和非血液学毒性明显更多，与A组相比，C组3 - 4级非血液学毒性明显更多。在QoL分析中未发现相关差异，但B组患者的食欲、呕吐和咯血有明显恶化。
由于试验提前终止，该试验没有达到计划的统计学效力。然而，现有数据不支持以多西他赛为基础的联合化疗作为晚期NSCLC二线治疗的作用。
