Grigorescu Alexandru, Ciuleanu Tudor, Firoiu Elena, Muresan Delia Ruta, Teodorescu Gabriela, Basson Bruce R
Department of Medical Oncology, Bucharest Oncology Institute, Bucharest, Romania.
Lung Cancer. 2007 Aug;57(2):168-74. doi: 10.1016/j.lungcan.2007.03.010. Epub 2007 Apr 30.
Third-generation platinum-based combinations are established as first-line treatment for advanced non-small cell lung cancer (NSCLC). Non-platinum regimens could be an alternative if they show similar efficacy with better tolerability. This randomized phase II trial compared the objective tumor response rate (ORR) of sequential gemcitabine plus vinorelbine followed by gemcitabine plus ifosfamide versus gemcitabine plus cisplatin. Secondary objectives included time to disease progression (TTP), overall survival and toxicity.
Chemo-naive patients with stages III and IV NSCLC and Karnofsky performance status >70 were assigned to receive either (a) gemcitabine 1000mg/m(2) plus vinorelbine 25mg/m(2) on days 1 and 8 for 2 cycles, followed by gemcitabine 1000mg/m(2) on days 1 and 8 plus ifosfamide 2000mg/m(2) on day 1 (GV-GI arm) for 2 cycles or (b) gemcitabine 1250mg/m(2) on days 1 and 8 with cisplatin 70mg/m(2) on day 1 (GC arm) for 4 cycles.
Between July 2001 and January 2003, 102 patients were enrolled (50 on the GV-GI arm and 52 on the GC arm). Patient characteristics were balanced between arms (GV-GI arm: median age 59 years, 84% male, 22 stage IIIB, 24 stage IV, 4 stage IIIA; GC arm: median age 56 years, 87% male, 27 stage IIIB, 23 stage IV, 2 stage IIIA). Of the 101 patients evaluable for response, ORR was significantly higher on the GC arm than on the GV-GI arm (25% versus 6%, respectively; p=0.007). No complete responses occurred. TTP was longer on the GC arm than on the GV-GI arm (median 135 and 79 days, respectively), although this difference was not statistically significant (p=0.065). Survival was not significantly different between the arms (median 293 and 197 days, respectively; p=0.16). Although significantly more thrombocytopenia was reported on the GC arm (22% and 4%, respectively; p=0.02), it did not lead to more transfusions (15 transfusions in 5 patients versus 14 transfusions in 6 patients, respectively). There was no significant difference in other safety parameters between treatment arms.
GC appears to produce better response in advanced NSCLC than GV-GI, with a trend towards longer TTP. Except for more thrombocytopenia with GC, similar toxicity profiles were observed.
第三代铂类联合方案已被确立为晚期非小细胞肺癌（NSCLC）的一线治疗方案。如果非铂类方案显示出相似疗效且耐受性更好，那么它们可以作为替代方案。这项随机II期试验比较了序贯吉西他滨加长春瑞滨后接吉西他滨加异环磷酰胺与吉西他滨加顺铂的客观肿瘤缓解率（ORR）。次要目标包括疾病进展时间（TTP）、总生存期和毒性。
既往未接受过化疗、美国东部肿瘤协作组（ECOG）体能状态评分＞70分的III期和IV期NSCLC患者被随机分配接受以下治疗之一：（a）第1天和第8天给予吉西他滨1000mg/m²加长春瑞滨25mg/m²，共2个周期，随后第1天和第8天给予吉西他滨1000mg/m²，第1天给予异环磷酰胺2000mg/m²（GV-GI组），共2个周期；或（b）第1天和第8天给予吉西他滨1250mg/m²，第1天给予顺铂70mg/m²（GC组），共4个周期。
2001年7月至2003年1月期间，共入组102例患者（GV-GI组50例，GC组52例）。两组患者特征均衡（GV-GI组：中位年龄59岁，男性占84%，IIIB期22例，IV期24例，IIIA期4例；GC组：中位年龄56岁，男性占87%，IIIB期27例，IV期23例，IIIA期2例）。在101例可评估疗效的患者中，GC组的ORR显著高于GV-GI组（分别为25%和6%；p=0.007）。未出现完全缓解。GC组的TTP长于GV-GI组（分别为中位135天和79天），尽管这一差异无统计学意义（p=0.065）。两组患者的生存期无显著差异（分别为中位293天和197天；p=0.16）。尽管GC组报告的血小板减少症显著更多（分别为22%和4%；p=0.02），但并未导致更多输血（分别为5例患者输血15次和6例患者输血14次）。治疗组之间的其他安全参数无显著差异。
与GV-GI方案相比，GC方案在晚期NSCLC中似乎能产生更好的缓解，且有TTP更长的趋势。除了GC方案导致更多血小板减少症外，观察到相似的毒性特征。
