White S C, Cheeseman S, Thatcher N, Anderson H, Carrington B, Hearn S, Ross G, Ranson M
Department of Medical Oncology, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
Clin Cancer Res. 2000 Mar;6(3):868-73.
This study was designed to assess the activity of oral topotecan (TPT) in patients with advanced non-small cell lung cancer previously untreated with chemotherapy. Eligible patients had inoperable stage III or stage IV non-small cell lung cancer and were chemotherapy-naive. Other inclusion criteria were Eastern Cooperative Oncology Group performance status 0, 1, or 2, adequate bone marrow, and renal and hepatic function. Of 30 patients, 29 were assessable for response. Oral TPT was administered for 5 days every 21 days for up to six cycles unless disease progression or unacceptable toxicity occurred. Patients received a dose of 2.3 mg/m2/day for the first cycle. Dose modification for subsequent cycles was based on tolerability. Patients completed symptom questionnaires every 3 weeks. Pharmacokinetics were evaluated in all patients during cycle 1. Three patients had radiological responses with a reduction in tumor size of 30-40%. No patients achieved complete or partial responses to treatment. Thirteen patients had a stable disease (43.3%), and the median survival was 39.9 weeks with a 1-year survival of 33.3%. At the time of analysis, 27 patients had died. Median time to progression was 12.3 weeks. Treatment was well tolerated. A total of 125 cycles of treatment were completed. Twelve patients (40%) experienced grade III/IV neutropenia. Five patients (16.6%) had grade III/IV anemia. There were two episodes of grade III/IV thrombocytopenia. The main nonhematological toxicities consisted of grade III nausea (13%) and grade III vomiting (13%). The most frequently reported disease-related symptoms at baseline were dyspnea, cough, and fatigue. There was a subsequent improvement in patient scores of dyspnea in 17% of patients, 31% showed improvement in cough, and 32% showed improvement in fatigue. The mean area under the curve of TPT following 2.3 mg/m2 p.o. was 51.6 ng.h/ml (%SD, 25%). The area under the curve of TPT on day 1 of the first cycle was correlated with the percentage fall in leukocytes. Although oral TPT at the applied dose and schedule showed modest activity as a single agent, almost one-half of the patients had a stable disease, and median time to progression was 12.3 weeks. The overall median survival was a promising 39.9 weeks, and useful palliation of symptoms was seen.
本研究旨在评估口服拓扑替康（TPT）在先前未接受过化疗的晚期非小细胞肺癌患者中的活性。符合条件的患者患有无法手术的III期或IV期非小细胞肺癌且未接受过化疗。其他纳入标准包括东部肿瘤协作组体能状态为0、1或2，骨髓、肾和肝功能良好。30例患者中，29例可评估疗效。口服TPT每21天给药5天，最多6个周期，除非疾病进展或出现不可接受的毒性。患者在第一个周期接受的剂量为2.3mg/m²/天。后续周期的剂量调整基于耐受性。患者每3周完成症状问卷。在第1周期对所有患者进行药代动力学评估。3例患者有放射学反应，肿瘤大小缩小30 - 40%。没有患者达到治疗的完全或部分缓解。13例患者疾病稳定（43.3%），中位生存期为39.9周，1年生存率为33.3%。在分析时，27例患者已死亡。中位疾病进展时间为12.3周。治疗耐受性良好。共完成125个周期的治疗。12例患者（40%）出现III/IV级中性粒细胞减少。5例患者（16.6%）出现III/IV级贫血。有2例III/IV级血小板减少事件。主要的非血液学毒性包括III级恶心（13%）和III级呕吐（13%）。基线时最常报告的与疾病相关的症状是呼吸困难、咳嗽和疲劳。随后，17%的患者呼吸困难评分有所改善，31%的患者咳嗽有所改善，32%的患者疲劳有所改善。口服2.3mg/m²后TPT的平均曲线下面积为51.6ng·h/ml（%标准差，25%）。第一个周期第1天TPT的曲线下面积与白细胞下降百分比相关。尽管按所应用的剂量和给药方案口服TPT作为单一药物显示出适度活性，但几乎一半的患者疾病稳定，中位疾病进展时间为12.3周。总体中位生存期为有前景的39.9周，且观察到症状得到有效缓解。
