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目的:观察卢比替康片在人体的安全性,确定卢比替康片口服给药对肿瘤患者的最大耐受剂量(MTD)及剂量限制性毒性(DLT),为Ⅱ期临床研究提供安全有效的给药剂量及方案。另外初步观察卢比替康的抗肿瘤疗效。方法:共纳入23例晚期恶性肿瘤患者。研究分为单次给药和连续给药两部分。19例患者,分5个剂量组(0.75,1.5,2.5,3.75,5.0 mg.m-2)单次口服卢比替康片,待清除期(7 d)后,患者再接受每日1次,每周连续5 d,停2 d的连续给药方案,所对应接受的连续给药剂量为:0.5,1.0,1.3,1.5和1.8mg.m-2.d-1。其余4例患者仅进行连续给药研究,给药剂量为2.0 mg.m-2.d-1。结果:卢比替康片经口服后患者主要不良反应为消化道反应(表现为恶心、呕吐和食欲减退)、乏力、骨髓抑制,另外观察到的不良反应还包括:腹泻、发热、头晕、肝功能异常和尿常规异常。单次给药研究中,共19例患者单次服药后均未出现DLT,但因考虑到单次给药方式并非今后临床治疗的给药方式,因此未再继续进行。在连续给药第6剂量组(2.0 mg.m-2.d-1)出现DLT,MTD为1.8 mg.m-2.d-1。本研究共20例患者可评价肿瘤疗效,疗效评价:PR1例(5%),SD 8例(40%),PD 11例(55%)。结论:卢比替康用于治疗晚期恶性肿瘤患者耐受性良好,人体对卢比替康的MTD为1.8 mg.m-2.d-1。
OBJECTIVE: To observe the safety of rubidium tablets in human body and to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for oral administration of rubidotek tablets to cancer patients, so as to provide a safe and effective method for phase Ⅱ clinical studies Dosage and program. In addition, preliminary observation of the anti-tumor effect of rubitecan. Methods: A total of 23 patients with advanced malignancies were enrolled. The study divided into single administration and continuous administration of two parts. Nineteen patients received a single oral dose of lubitidine tablets in five dose groups (0.75, 1.5, 2.5, 3.75, 5.0 mg.m -2) until the elimination phase (7 days) Continuous weekly dosing for 5 days and continuous d for 2 d resulted in continuous doses of 0.5, 1.0, 1.3, 1.5 and 1.8 mg.m-2.d-1, respectively. The remaining 4 patients were only given continuous drug administration at a dose of 2.0 mg.m-2.d-1. RESULTS: The main adverse reactions of patients receiving lubitidine after oral administration were gastrointestinal reactions (manifested as nausea, vomiting and loss of appetite), fatigue and bone marrow suppression. Other adverse reactions observed included diarrhea, fever, dizziness, liver function Abnormalities and abnormal urine. In the single-dose study, a total of 19 patients did not develop DLT after a single dose, but did not proceed because they considered that single administration was not a clinical modality of administration. DLT appeared in the sixth dose group (2.0 mg.m-2.d-1) continuously, with a MTD of 1.8 mg.m-2.d-1. Twenty patients in this study were evaluated for the efficacy of the therapy. The efficacy was evaluated in 1 PR (5%), 8 (40%) SD, and 11 (55%) PD. CONCLUSIONS: Lubituken is well tolerated in patients with advanced malignancies and has a MTD of 1.8 mg.m-2.d-1 for lubibitan in humans.