A Phase I Study of Mistletoe Extract

槲寄生提取物的一期研究

• 批准号: 7129534
• 负责人: Patrick J Mansky
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7129534
• 关键词: alternative medicine; angiosperms; clinical trial phase I; combination cancer therapy; drug interactions; drug screening /evaluation; gemcitabine; gene expression; human subject; human therapy evaluation; immune response; neoplasm /cancer chemotherapy; neoplasm /cancer nutrition therapy; patient oriented research; pharmacokinetics; plant extracts

During the past 80 years, plant extracts of the European mistletoe Viscum album L. have been widely used for cancer treatment in European countries. Preclinical data suggest immunostimulatory and other immunomodulatory effects of this plant extract. In clinical practice, mistletoe extracts have been used in cancer patients as sole intervention or as adjunct to conventional cancer therapies. Clinical efficacy in the treatment of cancer is an area of active investigation, with inconclusive results to date, due in large part to the use of varying preparations, concentrations, study populations and regimens. Moreover, little is known about the toxicity of mistletoe and the potential for botanical and drug interactions between mistletoe extract and standard chemotherapeutic agents. Gemcitabine is an approved antimetabolite chemotherapeutic agent with demonstrated single agent efficacy in the treatment of a wide range of solid tumors. Because the metabolism and pharmacokinetics of gemcitabine are well characterized, it is a chemotherapeutic agent well suited for the study of botanical/drug interactions in cancer therapy. The goals of this study are to investigate in a two-step phase I dose escalation design the effect of a highly purified mistletoe extract on the pharmacokinetics, pharmacodynamics, and safety of gemcitabine.. Pharmacokinetic toxicity profiles of gemcitabine in combination with mistletoe, neutrophil recovery, cytokine gene expression, and serum levels of markers of immune activation will be investigated in 40-50 patients with advanced solid tumors. The study aims at establishing a paradigm for the investigation of botanicals used in conjunction with standard cancer chemotherapy in complementary cancer medicine. To date, stage I of the study has been completed after enrollment of 20 patients without observing any DLT. Stage II of the study was initiated on 5/2005. A total of 27 patients have been enrolled . One DLT for gemcitabine (grade 4 neutropenia) has been observed at the gemcitabine dose level 6 (900 mg/m2). Therefore the dose level 6 cohort has been expanded to 6 patients. 4 patient had a partial response to therapy sustained for at least 3 cycles, 6 patients had stable disease on therapy for more than 9 weeks.

过去80年来，欧洲槲寄生Viscum album L.的植物提取物已在欧洲国家广泛用于癌症治疗。临床前数据表明这种植物提取物具有免疫刺激和其他免疫调节作用。在临床实践中，槲寄生提取物已被用于癌症患者作为单独的干预措施或作为传统癌症治疗的辅助手段。癌症治疗的临床疗效是一个正在积极研究的领域，迄今为止尚未得出结论，这在很大程度上是由于使用了不同的制剂、浓度、研究人群和治疗方案。此外，人们对槲寄生的毒性以及槲寄生提取物与标准化疗药物之间的植物和药物相互作用的可能性知之甚少。吉西他滨是一种经批准的抗代谢化疗药物，在治疗多种实体瘤方面已证明单药疗效。由于吉西他滨的代谢和药代动力学已得到充分表征，因此它是一种非常适合研究癌症治疗中植物/药物相互作用的化疗药物。本研究的目的是在两步 I 期剂量递增设计中研究高度纯化的槲寄生提取物对吉西他滨药代动力学、药效学和安全性的影响。吉西他滨与槲寄生联合用药的药代动力学毒性特征、中性粒细胞恢复、细胞因子基因表达以及免疫激活标志物的血清水平将在 40-50 名晚期实体瘤患者中进行研究。该研究旨在建立一个范例，用于研究在补充癌症医学中与标准癌症化疗结合使用的植物药。迄今为止，在招募了 20 名患者后，该研究的第一阶段已经完成，未观察到任何 DLT。第二阶段研究于 5/2005 开始。共有 27 名患者入组。在吉西他滨剂量水平 6 (900 mg/m2) 下观察到一种吉西他滨 DLT（4 级中性粒细胞减少症）。因此，剂量水平 6 队列已扩大至 6 名患者。 4 名患者对持续至少 3 个周期的治疗有部分反应，6 名患者治疗超过 9 周病情稳定。