Armstrong Deborah K, Spriggs David, Levin Jeremey, Poulin Ruth, Lane Stephen
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
Oncologist. 2005 Oct;10(9):686-94. doi: 10.1634/theoncologist.10-9-686.
The purpose was to conduct an integrated analysis of the cumulative hematologic toxicity of topotecan in patients with relapsed ovarian cancer and small cell lung cancer (SCLC). Data were pooled from eight phase II and phase III clinical studies performed in patients with relapsed stage III/IV ovarian cancer or extensive SCLC treated with topotecan at a dose of 1.5 mg/m(2) per day on days 1-5 of a 21-day course. Quantitative hematologic toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. A total of 4,124 courses of therapy was administered to the 879 patients in the pooled population. Grade 4 neutropenia was experienced by 78% of patients. The lowest nadirs for neutrophils and platelets generally occurred after the first course of therapy, followed by improvement or stabilization in subsequent courses. Neutropenia was noncumulative. During the first course, significant risk factors were identified: renal impairment and advanced age (grade 3/4 thrombocytopenia and grade 4 neutropenia) and prior radiotherapy; performance status score > or =2; SCLC; and exposure to both cisplatin (Platinol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin; Bristol-Myers Squibb) (grade 3/4 thrombocytopenia only). The most frequent interventions for hematologic toxicities were RBC transfusions, treatment delays, G-CSF support, and dose reductions. Analysis of neutrophil and platelet nadirs and dosing for each course of therapy showed no apparent evidence of cumulative neutropenia or thrombocytopenia. The risk of grade 3 or 4 anemia was higher during the first four courses of therapy and may need to be more aggressively managed with erythropoietin therapy.
目的是对拓扑替康在复发性卵巢癌和小细胞肺癌（SCLC）患者中的累积血液学毒性进行综合分析。数据来自八项II期和III期临床研究，这些研究在复发性III/IV期卵巢癌或广泛期SCLC患者中进行，患者接受拓扑替康治疗，剂量为每天1.5mg/m²，在21天疗程的第1 - 5天给药。使用美国国立癌症研究所通用毒性标准评估定量血液学毒性。汇总人群中的879名患者共接受了4124个疗程的治疗。78%的患者出现4级中性粒细胞减少。中性粒细胞和血小板的最低谷值通常在第一个疗程后出现，随后在后续疗程中有所改善或稳定。中性粒细胞减少无累积性。在第一个疗程中，确定了显著的风险因素：肾功能损害和高龄（3/4级血小板减少和4级中性粒细胞减少）以及既往放疗；体能状态评分≥2；SCLC；以及同时接触顺铂（顺铂；百时美施贵宝公司，新泽西州普林斯顿，http://www.bms.com）和卡铂（卡铂；百时美施贵宝公司）（仅3/4级血小板减少）。血液学毒性最常见的干预措施是红细胞输注、治疗延迟、粒细胞集落刺激因子支持和剂量减少。对每个疗程的中性粒细胞和血小板谷值以及给药情况的分析显示，没有明显证据表明存在累积性中性粒细胞减少或血小板减少。在治疗的前四个疗程中，3级或4级贫血的风险较高，可能需要更积极地用促红细胞生成素治疗。
