【摘要】 目的:探讨榄香烯乳剂注射液的不良反应,探索最大耐受剂量,为Ⅱ期临床研究推荐最佳剂量。方法:设置6个剂量组,每组入选3例患者。初始剂量750 mg·d-1,递增幅度250 mg,最高剂量2 000 mg·d-1。采用持续静脉滴注,qd,每周连续给药5 d,休息2d,28 d为一周期。按照世界卫生组织(WHO)抗肿瘤药物常见毒性反应分级标准及加拿大通用毒性评价标准(NCIC-CTC)评价不良反应,并初步观察疗效。结果:19例患者参加了临床试验,主要不良反应为三酰甘油及胆固醇水平升高,其余可见非感染性发热、消化道反应、白细胞下降等。不良反应与剂量升高无相关趋势。直到2 000 mg·d-1仍没有摸索到最大耐受剂量。根据耐受及生存情况,1 250 mg·d-1为合理使用剂量。结论:榄香烯乳剂注射液耐受性良好,结合生存情况,临床推荐1 250 mg·d-1为Ⅱ期临床使用剂量。更多还原

【Abstract】 Objective: To determine the maximum-tolerated dose ( MTD) , toxicity profile and and recommendation dose of elemene in phase II clinical trial. Methods: Patients with advanced cancers were assigned into cohorts of three participants at each dose level. Initial dosage participants were intravenously infused with was 750 mg·d-1 . The following cohort of participants was treated with an increased dose of 250 mg of elemene. The maximum cohort of participant was infused with a dose of up to 2 000 mg daily. Each cohort of participants was treated once daily for 5 days and then had a break for 2 days, totaling a 28-day cycle of therapy. Sequential dose levels were studied in the absence of dose-limiting toxicity (DLT) in the previous level. The toxicities were evaluated based on Word Health Organization Toxicity Grading Scale together with National Cancer Institute of Canada Common Toxicity Criteria (NCIC-CTC). Results; A total of 19 advanced cancer patients was enrolled in the trial. The most common treatment-emergent adverse effects were increases of triglyceride (TG) and total cholesterol (CHOL) levels. Other adverse events included febrile non-neutropenia, gastro-intestinal dysfunction and leucopoenia. No correlation was found between the toxicities with the dose level. A clinically defined MTD was not reached e-ven up to dose of 2 000 mg·d-1 . Conclusion; Elemene was well tolerated in the trial setting and the recommendation dose of phase II trial was 1 250 mg·d-1.更多还原