A Phase I Study of Mistletoe Extract on PK, PD, and Safety of Gemcitabine in CA

槲寄生提取物对吉西他滨在 CA 中的 PK、PD 和安全性的 I 期研究

基本信息

批准号：
7592496
负责人：
Patrick J Mansky
金额：
$ 97.4万
依托单位：
依托单位国家：
美国
项目类别：
财政年份：
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/7592496
关键词：
Acute Kidney Failure Antimetabolites Area Botanicals Cancer Patient Cellulitis Chemotherapy-Oncologic Procedure Clinical Colorectal Cancer Country Cytokine Gene Data Data Analyses Dose Drug Interactions Drug Kinetics Enrollment European Gemcitabine/Mistletoe Gene Expression Goals Immunologic Markers Intervention Investigation Malignant Neoplasms Malignant neoplasm of pancreas Medicine Metabolism Mistletoe Mistletoe preparation Neutropenia Non-Small-Cell Lung Carcinoma Patients Pharmacodynamics Phase Phase I Clinical Trials Plant Extracts Population Study Preparation Range Recovery Safety Serum Solid Neoplasm Standards of Weights and Measures Thrombocytopenia Toxic effect Treatment Protocols Viscum album cancer therapy chemotherapeutic agent clinical efficacy design experience gemcitabine malignant breast neoplasm neutrophil pre-clinical

项目摘要

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. The study completed accrual in July 2007 after enrolling 44 patients: 17 patients had colorectal cancer, 12 breast cancer, 8 pancreatic cancer and 4 NSCLC, respectively. Patients experienced 4 DLTs, including grade 4 neutropenia, grade 4 thrombocytopenia, grade 4 acute renal failure and grade 3 cellulitis . The MTD for the combination regimen of mistletoe and gemcitabine was established at gemcitabine dose level 8: 1300 mg/ m2 and mistletoe 250 mg s.c. The study is now closed to accrual and data analysis is ongoing.

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升级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，中性粒细胞恢复，细胞因子基因表达和免疫激活标志物的血清水平水平相结合的药代动力学毒性谱图在40-50例晚期实质性瘤患者中进行研究。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。这项研究于2007年7月完成44例患者后完成应计：17例患者患有大肠癌，12例乳腺癌，8例胰腺癌和4例NSCLC。患者经历了4种DLT，包括4级中性粒细胞减少症，4级血小板减少症，4级急性肾功能衰竭和3级蜂窝织炎。在吉西他滨剂量8：1300 mg/ m2和槲寄生250 mg S.C.该研究现已关闭，并正在进行数据分析。