Institut für Experimentelle Onkologie und Therapieforschung, Technische Universität München, Germany.
Clin Appl Thromb Hemost. 2012 Mar-Apr;18(2):159-65. doi: 10.1177/1076029611433769. Epub 2012 Jan 23.
In 2 double-blind studies, ambulatory patients with objectively proven, disseminated metastatic breast carcinoma (TOPIC-1) or stage III/IV non-small-cell lung carcinoma (TOPIC-2) were randomized to certoparin 3000 IU or placebo subcutaneously once daily, for 6 months. Primary efficacy outcome was objectively confirmed symptomatic or asymptomatic venous thromboembolism (VTE). Safety outcomes included bleeding (major and minor), and thrombocytopenia. TOPIC-1 was halted after an interim analysis. Venous thromboembolism occurrence was not different between treatment groups in TOPIC-1 (4% treated with certoparin, 7 of 174 vs 4% receiving placebo, 7 of 177, odds ratio [OR] 1.02; 95% confidence interval [CI] 0.30-3.48) and in TOPIC-2 (4.5%, 12 of 268) vs 8.3%, 22 of 264, respectively, OR 0.52; CI 0.23-1.12). Mortality was not different between groups. A post hoc analysis showed certoparin significantly reduced VTE in stage IV lung carcinoma (3.5% vs 10.2%; P = .032) without increased bleeding. In conclusion, thrombosis risk and prophylactic benefit was highest in stage IV lung carcinoma patients.
在 2 项双盲研究中，经客观证实患有转移性乳腺癌（TOPIC-1）或 III/IV 期非小细胞肺癌（TOPIC-2）的门诊患者被随机分配至接受依诺肝素 3000IU 或安慰剂皮下注射，每天 1 次，持续 6 个月。主要疗效终点为客观证实的有症状或无症状静脉血栓栓塞症（VTE）。安全性结局包括出血（主要和次要）和血小板减少症。TOPIC-1 在中期分析后停止。TOPIC-1 中治疗组之间静脉血栓栓塞症发生率无差异（依诺肝素组为 4%，174 例中有 7 例；安慰剂组为 4%，177 例中有 7 例，比值比[OR]为 1.02；95%置信区间[CI]为 0.30-3.48）和 TOPIC-2（4.5%，268 例中有 12 例；8.3%，264 例中有 22 例，OR 为 0.52；CI 为 0.23-1.12）。两组死亡率无差异。事后分析显示，依诺肝素可显著降低 IV 期肺癌患者的 VTE（3.5% vs 10.2%；P =.032），而不增加出血。总之，血栓形成风险和预防获益在 IV 期肺癌患者中最高。
