Bélanger Karl, MacDonald David, Cairncross Gregory, Gertler Stan, Forsyth Peter, Burdette-Radoux Susan, Bergeron Julie, Soulières Denis, Ludwin Samuel, Wainman Nancy, Eisenhauer Elizabeth
Department of Hematology, CHUM-Hôpital Notre-Dame, Montreal, Quebec, Canada.
Invest New Drugs. 2003 Nov;21(4):473-80. doi: 10.1023/a:1026211620793.
To determine the efficacy and toxicity of a novel chemotherapeutic approach with topotecan, a camptothecin analog, for progressive or recurring anaplastic oligodendroglioma or mixed oligoastrocytoma.Patients from seven centers with recurrent or progressive disease were treated with topotecan, 1.5 mg/m(2) intravenously (i.v.), 30 min dailyx5 days every 3 weeks. Efficacy and toxicity were assessed clinically and radiologically. The study was planned to accrue up to 30 evaluable patients if there was at least one response among the first 15 patients treated. Sixteen eligible patients entered the study. No response was documented in 14 evaluable patients. Eleven patients had stable disease of a median of 3.8 months and three had progressive disease. Sixteen patients were evaluable for toxicity. The most significant toxic effect was myelosuppression. Grade 3 or 4 granulocytopenia was experienced by 15 of 16 patients and led to dose reduction in nearly half of the cycles delivered. Other adverse effects were fatigue, nausea, stomatitis, alopecia, and vomiting.Topotecan, delivered in the dailyx5 regimen, is relatively well tolerated. We could not demonstrate significant activity among the population studied to justify completing accrual to 30 patients. Topotecan did not demonstrate, with this small sample size, efficacy as a salvage chemotherapy monotherapy after exposure to procarbazine, CCNU and vincristine. Further trials with different agents in this indication are certainly warranted.
为确定新型化疗方法——拓扑替康(一种喜树碱类似物)治疗进展性或复发性间变性少突胶质细胞瘤或混合性少突星形细胞瘤的疗效及毒性。来自七个中心的复发或进展性疾病患者接受拓扑替康治疗,剂量为1.5mg/m²静脉注射,每日30分钟,共5天,每3周重复一次。通过临床及影像学评估疗效和毒性。该研究计划如果在前15例接受治疗的患者中至少有一例有反应,则纳入多达30例可评估患者。16例符合条件的患者进入研究。14例可评估患者中未记录到反应。11例患者病情稳定,中位时间为3.8个月,3例病情进展。16例患者可评估毒性。最显著的毒性作用是骨髓抑制。16例患者中有15例出现3级或4级粒细胞减少,近半数疗程因此而减量。其他不良反应包括疲劳、恶心、口腔炎、脱发和呕吐。每日×5方案给药的拓扑替康耐受性相对良好。在研究人群中,我们未能证明有显著活性以支持纳入30例患者。在这个小样本中,拓扑替康作为在接受丙卡巴肼、洛莫司汀和长春新碱治疗后的挽救性化疗单药治疗,未显示出疗效。对于该适应证,肯定需要进一步用不同药物进行试验。