A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer
A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer
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DOI：
10.1111/j.1538-7836.2004.00871.x
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发表时间：
2004-08-01
影响因子：
10.4
通讯作者：
Soyuer, S
中科院分区：
文献类型：
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作者：
Altinbas, M;Coskun, HS;Soyuer, S
背景小细胞肺癌（SCLC）是一种对化疗有反应的肿瘤类型，但大多数患者最终都会经历疾病进展。SCLC与凝血系统的改变有关。目前的随机临床试验（RCT）旨在确定与单独使用CT相比，在联合化疗（CT）中加入低分子量肝素（LMWH）是否会改善SCLC的结局。方法环磷酰胺、表柔比星和长春新碱联合化疗，每3周1次，共6个周期。84例患者随机接受单独CT（n=42）或CT + LMWH（n=42）。LMWH包括在18周CT期间每日一次给予5000 U剂量的达肝素。结果单用CT组总有效率为42.5%，CT + LMWH组总有效率为69.2%（P=0.07）。单独使用CT的中位无进展生存期为6.0个月，使用CT加LMWH的中位无进展生存期为10.0个月（P=0.01）。中位总生存期为8.0个月，单独CT和13.0个月，CT + LMWH（P=0.01）。LMWH治疗在有限和广泛疾病阶段的患者中也出现了类似的生存改善。CT+LMWH组相对于CT组的死亡风险为0.56（95%置信区间0.30，0.86）（对数秩检验P=0.012）。实验处理的毒性极低，无处理相关死亡。结论这些结果支持抗凝剂，特别是LMWH，可以改善小细胞肺癌的临床结局。这种相对无毒的治疗方法的进一步临床试验表明。
Background Small cell lung cancer (SCLC) is a chemotherapy-responsive tumor type but most patients ultimately experience disease progression. SCLC is associated with alterations in the coagulation system. The present randomized clinical trial (RCT) was designed to determine whether addition of low-molecular-weight heparin (LMWH) to combination chemotherapy (CT) would improve SCLC outcome compared with CT alone. Methods Combination CT consisted of cyclophosphamide, epirubicine and vincristine (CEV) given at 3-weekly intervals for six cycles. Eighty-four patients were randomized to receive either CT alone (n=42) or CT plus LMWH (n=42). LMWH consisted of dalteparin given at a dose of 5000 U once daily during the 18 weeks of CT. Results Overall tumor response rates were 42.5% with CT alone and 69.2% with CT plus LMWH (P=0.07). Median progression-free survival was 6.0 months with CT alone and 10.0 months with CT plus LMWH (P=0.01). Median overall survival was 8.0 months with CT alone and 13.0 months with CT plus LMWH (P=0.01). Similar improvement in survival with LMWH treatment occurred in patients with both limited and extensive disease stages. The risk of death in the CT+LMWH group relative to that in the CT group was 0.56 (95% confidence interval 0.30, 0.86) (P=0.012 by log rank test). Toxicity from the experimental treatment was minimal and there were no treatment-related deaths. Conclusions These results support the concept that anticoagulants, and particularly LMWH, may improve clinical outcomes in SCLC. Further clinical trials of this relatively non-toxic treatment approach are indicated.