...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Clinical Oncology >Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ZD1839 Is Generally Well-Tolerated and Has Activity in Non-Small-Cell Lung Cancer and Other Solid Tumors: Results of a Phase I Trial.
【24h】

Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ZD1839 Is Generally Well-Tolerated and Has Activity in Non-Small-Cell Lung Cancer and Other Solid Tumors: Results of a Phase I Trial.

机译：选择性口服表皮生长因子受体酪氨酸激酶抑制剂ZD1839通常耐受性良好，并且在非小细胞肺癌和其他实体瘤中具有活性：I期试验的结果。

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

PURPOSE: To investigate safety, tolerability, dose-related pharmacologic properties, and pharmacodynamics of ZD1839 (gefinitib, Iressa; AstraZeneca Pharmacueticals, Wilmington, DE), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with solid tumor types known to express or highly express EGFR. METHODS: This was an open-label, phase I, dose escalation safety/tolerability trial of oral ZD1839 (150 to 1,000 mg/d), administered once daily for 28-continuous-day cycles until disease progression or undue toxicity. RESULTS: Of 71 (69 assessable for safety; 58 for efficacy) patients at seven dose levels, most had non-small-cell lung (n = 39) or head and neck (n = 18) cancer, and 68 of 71 patients received prior cancer therapy (two or more regimens in 54 patients [78%]). Diarrhea and rash, the primary dose-limiting toxicities (DLTs), occurred at 800 mg. Frequent treatment-related grade 1/2 adverse events were diarrhea (55%), asthenia (44%), and acne-like follicular rash (46%). At doses >/= 800 mg, 45% of patients required dose reductions. No increased or cumulative toxicity was observed over 250 patient-months of exposure. Pharmacokinetic analysis showed that steady-state occurred by day 7, interpatient exposure was more variable than intrapatient exposure, and variability of exposure did not change with dose. One patient experienced a partial response, but antitumor activity manifested mainly as prolonged stable disease (45% of patients >/= 3 months, 22% >/= 6 months, and 7.2% >/= 1 year). No relationship between dose, response, or duration on study was observed. CONCLUSION: Rash and diarrhea, generally mild and tolerable at doses
机译：目的：研究表皮生长因子受体（EGFR）酪氨酸激酶抑制剂ZD1839（表皮生长因子受体（EGFR）酪氨酸激酶抑制剂）的安全性，耐受性，剂量相关的药理特性和药效学表达或高度表达EGFR。方法：这是一项口服ZD1839（150至1,000 mg / d）的开放式I期，剂量递增安全性/耐受性试验，每天给药一次，连续28天，直到疾病进展或出现不适当的毒性。结果：在七个剂量水平的71位患者（69位可评估安全性; 58位有效性）中，大多数患有非小细胞肺癌（n = 39）或头颈部癌（n = 18），在71位患者中有68位接受了治疗先前的癌症治疗（54例患者中的两种或更多种方案[78％]）。腹泻和皮疹是主要的剂量限制性毒性（DLT），剂量为800 mg。与治疗相关的常见1/2级不良反应为腹泻（55％），乏力（44％）和痤疮样滤泡性皮疹（46％）。在> / = 800 mg的剂量下，需要降低剂量的患者占45％。暴露250个月以上，未观察到毒性增加或累积。药代动力学分析表明，患者入院的第7天要比入院的患者稳定得多，而且入院的变异性不会随剂量的变化而变化。一名患者经历了部分缓解，但抗肿瘤活性主要表现为疾病持续时间延长（45％≥3个月，22％≥6个月和7.2％≥1年）。没有观察到剂量，反应或研究持续时间之间的关系。结论：皮疹和腹泻是轻度且可耐受的，剂量为600 mg / d时为DLT，最大剂量为800 mg / d。在所有剂量下均观察到抗肿瘤活性。药代动力学分析证实了每日一次口服给药的适用性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号