Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer

Vernon J. Harvey , Janet R. Hardy , Shelba Smith , William Grove , Bruce C. Baguley
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引用次数: 17

Abstract

CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino]-N,5-dimethyl-4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade ≥ 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade ≤ 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.

amsacrine类似物CI-921 (NSC 343499)治疗非小细胞肺癌的II期研究
Ci-921 (nsc 343499;9-[[2-甲氧基-4-[(甲基磺酰基)氨基]苯基]氨基]- n,5-二甲基-4-吖啶甲酰胺)是一种具有高抗肿瘤活性的拓扑异构酶ⅱ类毒素。16例可评估的非小细胞肺癌(NSCLC)患者(7例未接受过治疗,9例手术/放疗后复发)通过15分钟输注给药,剂量(648 mg/m2,分3天,每3周重复一次)由I期试验确定。患者的中位表现状态为1 (WHO),中位年龄为61岁。组织学包括鳞状癌(11例)、腺癌(1例)、混合组织学(2例)、细支气管肺泡癌(1例)和大细胞未分化癌(1例)。中性粒细胞减少≥3级15例,感染恢复3例,癫痫大发作1例。66%的疗程中出现≤2级恶心和呕吐,37%的疗程中出现静脉炎。1例鳞状细胞癌患者获得了持续5个月的部分缓解。进一步的测试,在这种和其他肿瘤类型使用多个每日时间表是必要的。
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