Phase III Study of Immediate Compared With Delayed Docetaxel After Front-Line Therapy With Gemcitabine Plus Carboplatin in Advanced Non-Small-Cell Lung Cancer
Phase III Study of Immediate Compared With Delayed Docetaxel After Front-Line Therapy With Gemcitabine Plus Carboplatin in Advanced Non-Small-Cell Lung Cancer
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DOI：
10.1200/jco.2008.17.1405
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发表时间：
2009-02-01
影响因子：
45.3
通讯作者：
Schiller, Joan H.
中科院分区：
文献类型：
--
作者：
Fidias, Panos M.;Dakhil, Shaker R.;Schiller, Joan H.
吉西他滨联合卡铂（GC）是晚期非小细胞肺癌（NSCLC）的一线治疗药物。对于没有进展的患者，二线化疗的最佳临床获益时机仍不确定。这项III期随机试验评估了多西他赛在胃癌后立即或在疾病进展时使用的有效性和安全性。患者和方法未接受化疗的患者为IIIB期非小细胞肺癌合并胸腔积液或IV期非小细胞肺癌。第1天和第8天给予吉西他滨（1,000 mg/m(2)），第1天给予卡铂（曲线下面积= 5）。在四个21天的周期后，没有进展的患者被随机分配到立即多西他赛组（每21天第1天多西他赛75mg /m2，最多6个周期）或延迟多西他赛组。主要终点是随机分配的总生存期（OS）。其他分析包括肿瘤反应、毒性、无进展生存期（PFS）和生活质量（QOL）。结果共纳入566例患者；398例完成GC；309例患者被随机分配到两个多西他赛治疗组。多西紫杉醇组的毒性大致相当。即刻多西他赛的中位PFS（5.7个月）显著高于延迟多西他赛（2.7个月）（P = 0.0001）。即刻多西他赛的中位OS（12.3个月）大于延迟多西他赛（9.7个月），但差异无统计学意义（P = 0.0853）。生活质量结果无统计学差异(P =。76)多西紫杉醇组间。结论：我们观察到一线GC后立即给予多西他赛的PFS有统计学意义的改善，OS有非统计学意义的增加，没有增加毒性或降低生活质量。
PurposeGemcitabine plus carboplatin (GC) is active as front-line treatment for advanced non-small-cell lung cancer (NSCLC). For patients without progression, timing of second-line chemotherapy for optimum clinical benefit remains uncertain. This phase III, randomized trial assessed the efficacy and safety of docetaxel administered either immediately after GC or at disease progression.Patients and MethodsThe chemotherapy-nave patients enrolled had either stage IIIB NSCLC with pleural effusion or stage IV NSCLC. Gemcitabine (1,000 mg/m(2)) was administered on days 1 and 8 followed by carboplatin (area under the curve = 5) on day 1. After four 21-day cycles, patients who did not have progression were randomly assigned either to an immediate docetaxel group (docetaxel 75 mg/m2 on day 1 every 21 days, with maximum of six cycles) or to a delayed docetaxel group. The primary end point was overall survival (OS) measured from random assignment. Additional analyses included tumor response, toxicity, progression-free survival (PFS), and quality of life (QOL).ResultsEnrollment totaled 566 patients; 398 patients completed GC; 309 patients were randomly assigned equally to the two docetaxel treatment groups. Toxicity profiles were generally comparable for the docetaxel groups. Median PFS for immediate docetaxel (5.7 months) was significantly greater (P = .0001) than for delayed docetaxel (2.7 months). Median OS for immediate docetaxel (12.3 months) was greater than for delayed docetaxel (9.7 months), but the difference was not statistically significant (P = .0853). QOL results were not statistically different (P =. 76) between docetaxel groups.ConclusionWe observed a statistically significant improvement in PFS and a nonstatistically significant increase in OS when docetaxel was administered immediately after front-line GC, without increasing toxicity or decreasing QOL.