A RANDOMIZED TRIAL OF ANTICOAGULATION WITH WARFARIN AND OF ALTERNATING CHEMOTHERAPY IN EXTENSIVE SMALL-CELL LUNG-CANCER BY THE CANCER AND LEUKEMIA GROUP-B
A RANDOMIZED TRIAL OF ANTICOAGULATION WITH WARFARIN AND OF ALTERNATING CHEMOTHERAPY IN EXTENSIVE SMALL-CELL LUNG-CANCER BY THE CANCER AND LEUKEMIA GROUP-B
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DOI：
10.1200/jco.1989.7.8.993
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发表时间：
1989-08-01
影响因子：
45.3
通讯作者：
GREEN, MR
中科院分区：
文献类型：
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作者：
CHAHINIAN, AP;PROPERT, KJ;GREEN, MR
癌症和白血病B组(CALGB)进行了一项前瞻性随机试验，以评估华法林和交替化疗在广泛性小细胞肺癌(SCCL)中的作用。在对患者的性别和表现状况进行分层后，患者被随机分配到接受甲氨蝶呤、阿霉素(Adria实验室，哥伦布，俄亥俄州)、环磷酰胺和洛莫司汀(MACC)(MACC)或MACC加华法林(MACC+W)或丝裂霉素、依托泊苷、顺铂和六甲基三聚氰胺替代MACC的化疗(MEPH/MACC)。持续给予华法林以维持凝血酶原时间为对照组的1.5到两倍。共有328名患者入选，294名患者可评价。与单纯MACC(8%和43%)或MEPH/MACC(10%和38%)相比，MACC+W组的客观有效率(完全缓解[CR]和部分缓解[PR]分别为17%和50%)在统计学上有显著优势(P=0.012)。MACC+W组的无失败生存期(P=0.054 Wilcoxon检验)和总生存期(P=0.098 Wilcoxon检验)均高于MACC(5.0个月和7.9个月)和Meph/MACC(5.0个月和7.9个月)。除了MACC+W的出血事件增加外，三种药物的毒性相似，其中4名患者(4%)危及生命，另外两名患者(2%)死亡。这些数据支持华法林在治疗SCCL中的作用，但没有建立其作用机制。华法林值得在SCCL中进一步研究，特别是在疾病有限的患者中。
The Cancer and Leukemia Group B (CALGB) conducted a prospective randomized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer (SCCL). After stratification for sex and and performance status, patients were randomly assigned to receive chemotherapy with methotrexate, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (CCNU) (MACC), or MACC plus warfarin (MACC + W), or mitomycin, etoposide, cisplatin, and hexamethylmelamine alterating with MACC (MEPH/MACC). Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values. A total of 328 patients were enrolled, and 294 were evaluable. There was a statistically significant advantage in objective response rates (complete [CR] and partial responses [PR], respectively) for MACC + W (17% and 50%) as compared with MACC alone (8% and 43%) or MEPH/MACC (10% and 38%) (P = .012). Both failure-free survival (P = .054 Wilcoxon test) and overall survival (P = .098 Wilcoxon test) were higher on MACC + W (median, 6.6 months and 9.3 months, respectively), as compared with MACC (5.0 months and 7.9 months) and MEPH/MACC (5.0 months and 7.9 months). Toxicity was comparable among the three arms, except for increased hemorrhagic events on MACC + W, which were life-threatening in four patients (4%), and lethal in two others (2%). These data support the role of warfarin in the treatment of SCCL, but do not establish its mechanism of action. Warfarin deserves further studies in SCCL, particularly in patients with limited disease.