Phase I Study of Mistletoe Extract and Gemcitabine

槲寄生提取物和吉西他滨的 I 期研究

• 批准号: 6959220
• 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/6959220
• 关键词: alternative medicine; antineoplastics; clinical trial phase I; combination chemotherapy; cytokine; cytokine receptors; dosage; drug adverse effect; drug interactions; drug screening /evaluation; gemcitabine; gene expression; human subject; human therapy evaluation; immune response; immunogenetics; medicinal plants; microarray technology; neoplasm /cancer; neoplasm /cancer chemotherapy; 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, a total of 15 patients have been enrolled on five mistletoe dose levels. No treatment-related SAEs have been observed. 1 patient had a partial response, 4 patients had stable disease on therapy for more than 9 weeks.

在过去的80年中，欧洲槲寄生粘液专辑L.的植物提取物已被广泛用于欧洲国家的癌症治疗。临床前数据表明该植物提取物的免疫刺激性和其他免疫调节作用。在临床实践中，槲寄生提取物已在癌症患者中用作唯一干预或与常规癌症疗法的辅助措施。癌症治疗中的临床功效是一个积极研究的领域，迄今为止的结果尚无定论，这在很大程度上是由于使用了不同的制剂，浓度，研究人群和方案。此外，关于槲寄生的毒性以及槲寄生提取物与标准化学治疗剂之间的植物和药物相互作用的潜力知之甚少。吉西他滨是一种批准的抗代谢物化学治疗剂，在治疗广泛的实体瘤中具有单一药物的功效。由于吉西他滨的代谢和药代动力学的特征很好，因此它是一种化学治疗剂，非常适合研究癌症治疗中的植物/药物相互作用。这项研究的目标是在两步阶段的剂量上升级设计中进行调查，高度纯化的槲寄生提取物对吉西他滨的药代动力学，药效学和安全性。 40-50例晚期实体瘤患者将研究，细胞因子基因表达和免疫激活标记的血清水平。该研究旨在建立一个范式，以研究与互补癌症医学中标准癌症化疗相结合的植物学。迄今为止，总共15名患者已入学五个槲寄生剂量水平。未观察到与治疗相关的SAE。 1名患者有部分反应，有4例患者在治疗中患有稳定的疾病超过9周。