PHASE-II STUDY OF TAXOL, MERBARONE, AND PIROXANTRONE IN STAGE-IV NON-SMALL-CELL LUNG-CANCER - THE EASTERN COOPERATIVE ONCOLOGY GROUP RESULTS
PHASE-II STUDY OF TAXOL, MERBARONE, AND PIROXANTRONE IN STAGE-IV NON-SMALL-CELL LUNG-CANCER - THE EASTERN COOPERATIVE ONCOLOGY GROUP RESULTS
复制标题
DOI：
10.1093/jnci/85.5.388
复制
发表时间：
1993-03-03
期刊：
影响因子：
--
通讯作者：
JOHNSON, D
中科院分区：
文献类型：
--
作者：
CHANG, AY;KIM, K;JOHNSON, D
背景：转移性（IV期）非小细胞肺癌患者通常预后不良，且化疗难治。三种新药紫杉醇、美巴龙和吡罗蒽醌在体外和动物体内显示出很有前途的抗肿瘤治疗作用。紫杉醇是一种抗微管剂，在细胞分裂过程中干扰有丝分裂。甲基巴龙是硫代巴比妥酸和苯胺的共轭物，是拓扑异构酶II抑制剂，因此抑制DNA合成和肿瘤生长。吡罗蒽醌是一种蒽二酮衍生物，是一种DNA嵌入剂，在动物研究中显示出有效的抗肿瘤活性。用途：我们的随机11期研究旨在评估这些药物治疗IV期转移性非小细胞肺癌的疗效和毒性。研究方法：符合条件的患者（119例）被随机分配接受每3周一次的三种治疗之一：250 mg/m2紫杉醇24小时静脉输注，1000 mg/m2美巴龙通过中心导管每天持续静脉输注5天，或150 mg/m2吡罗蒽醌1小时静脉输注。患者未接受化疗。每3周评价一次反应和毒性。结果：25名患者被随机分配接受紫杉醇治疗，47名接受美巴龙治疗，47名接受吡罗黄酮治疗。44例接受吡罗蒽醌治疗的可评估患者中有1例（2.3%）完全缓解。部分反应率分别为20.8%（24例患者中的5例）和5.7%（35例中的2例），可评估的患者用紫杉醇或美巴龙治疗。紫杉醇、美巴龙和吡罗蒽醌的一年生存率分别为41.7%、21.6%和22.6%，中位生存时间分别为24.1、19.9和29.3周。这些差异在统计学上并不显著，但这项研究并不是为了比较生存率。总体而言，毒性是可控的。术前用药时，未观察到紫杉醇过敏反应。最常见的毒性反应是紫杉醇或吡罗蒽醌治疗的白细胞减少症和甲基巴龙的血栓栓塞并发症。与治疗直接相关的死亡分别发生在4%（1例患者）、11.4%（4例）和5%（2例）接受紫杉醇、美巴龙和吡罗蒽醌治疗的可评估患者中。在所有三个组中仅偶尔发生神经毒性和神经毒性。结论：根据缓解率（20.8%部分缓解）和1年生存率（41.7%），紫杉醇是治疗转移性非小细胞肺癌的活性药物。Merbarone和piroxantrone相对不活跃。结论：紫杉醇的研究仍需进一步深入。在未来的研究中，紫杉醇应与其他药物联合使用，粒细胞集落刺激因子应用于改善骨髓抑制。
Background: Patients with metastatic (stage IV) non-small-cell lung cancer usually have a poor prognosis and disease refractory to chemotherapy. Three new agents-taxol, merbarone, and piroxantrone-have shown promising antitumor treatment in vitro and in animals. Taxol is an antimicrotubular agent that interferes with mitosis during cell division. Merbarone, a conjugate of thiobarbituric acid and aniline, is a topoisomerase II inhibitor, which thus inhibits DNA synthesis and tumor growth. Piroxantrone, an anthracenedione derivative, is a DNA intercalating agent that has shown potent antitumor activity in animal studies. Purpose: Our randomized phase 11 study was designed to evaluate the efficacy and toxicity of these agents in the treatment of stage IV metastatic non-small-cell lung cancer. Methods: Eligible patients (119) were randomly assigned to receive one of the three treatments given every 3 weeks: 250 mg/m2 taxol by a 24-hour intravenous infusion, 1000 mg/m2 merbarone by continuous intravenous infusion through a central catheter daily for 5 days, or 150 mg/m2 piroxantrone by intravenous infusion over 1 hour. Patients had received no chemotherapy. Response and toxicity were evaluated every 3 weeks. Results: Twenty-five patients were randomly assigned to receive taxol, 47 to receive merbarone, and 47 to receive piroxantrone. One of 44 assessable patients (2.3%) treated with piroxantrone had a complete response. Rates for partial response were 20.8% (five of 24 patients) and 5.7% (two of 35) for assessable patients treated with taxol or merbarone, respectively. One-year survival rates were 41.7%, 21.6%, and 22.6%, and median survival times were 24.1, 19.9, and 29.3 weeks for taxol, merbarone, and piroxantrone, respectively. These differences were not statistically significant, but this study was not designed to compare survival. In general, toxicity was manageable. With premedication, no anaphylaxis was observed with taxol. The most common toxic effects were leukopenia with taxol or piroxantrone treatment and thromboembolic complications with merbarone. Death directly related to treatment occurred in 4% (one patient), 11.4% (four), and 5% (two) of the assessable patients receiving taxol, merbarone, and piroxantrone, respectively. Cardiotoxicity and neurotoxicity occurred only occasionally in all three arms. Conclusion: On the basis of the response rate (20.8% partial response) and 1-year survival rate (41.7%), taxol is an active agent for the treatment of metastatic non-small-cell lung cancer. Merbarone and piroxantrone are relatively inactive. Implications: Further study of taxol is warranted. In future studies, taxol should be combined with other agents, and granulocyte colony-stimulating factor should be used to ameliorate myelosuppression.