Phase I and pharmacokinetic study of E7070, a novel sulfonamide, given at a daily times five schedule in patients with solid tumors. A study by the EORTC-Early Clinical Studies Group (ECSG)
Phase I and pharmacokinetic study of E7070, a novel sulfonamide, given at a daily times five schedule in patients with solid tumors. A study by the EORTC-Early Clinical Studies Group (ECSG)
复制标题
DOI：
10.1023/a:1012287111922
复制
发表时间：
2001-09-01
影响因子：
50.5
通讯作者：
Campone, M
中科院分区：
文献类型：
--
作者：
Punt, CJA;Fumoleau, P;Campone, M
背景：E7070 是一种新型抗肿瘤磺酰胺，可将细胞阻滞于 G1 期。启动了一项 I 期研究，以调查该化合物的毒性、最大耐受剂量 (MTD) 和药代动力学，每天一次，每三周一次，五次给药方案。 患者和方法：不适合标准治疗形式的实体瘤患者符合条件。 E7070按剂量水平给予3-6名患者的队列，起始剂量为10 mg/m(2)/天。根据类似斐波那契方案进行剂量递增。结果：33 名患者进入了研究。 E7070剂量为200和160 mg/m(2)/天时，发生了剂量限制性毒性，包括发热性中性粒细胞减少症、血小板减少症、腹泻、皮肤毛囊炎、乏力和口腔炎。 E7070在此方案中的药代动力学特征随着剂量的增加呈非线性。在接受过大量治疗的乳腺癌患者中观察到部分缓解。还记录了疾病稳定和一些轻微反应。结论：骨髓抑制是 E7070 的主要毒性。观察E7070的临床疗效。每日五次方案中进一步研究的推荐剂量为 130 mg/m(2)/天。
Background: E7070 is a novel antitumor sulfonamide which blocks the cell in G1 phase. A phase I study was initiated to investigate the toxicity, maximum tolerated dose (MTD), and pharmacokinetics of this compound when administered intravenously at a daily times five schedule once every three weeks.Patients and methods: Patients with solid tumors not amenable to standard forms of therapy were eligible. E7070 was administered to cohorts of 3-6 patients per dose level, the starting dose was 10 mg/m(2)/day. Dose escalation was performed according to a Fibonacci-like scheme.Results: Thirty-three patients entered the study. At E7070 doses of 200 and 160 mg/m(2)/day dose-limiting toxicities occurred, which consisted of febrile neutropenia, thrombocytopenia, diarrhea, skin folliculitis, asthenia, and stomatitis. The pharmacokinetic profile of E7070 at this schedule is non-linear with increasing dose. A partial response was observed in a patient with heavily pretreated breast cancer. Disease stabilizations and some minor responses were also documented.Conclusions: Myelosuppression is the predominant toxicity of E7070. Clinical efficacy with E7070 was observed. The recommended dose for further studies at this daily times five schedule is 130 mg/m(2)/day.