Phase Ⅰ human tolerability trial of rubitecan tablets

ZHANG Wen; WANG Jin-wan; CUI Cheng-xu; YANG Lin; SONG Yan; SUN Yong-kun

Abstract：Objective:To investigate the tolerability of rubitecan tablets in patients with advanced malignant tumors,and to determine the maximal tolerated dose(MTD)and recommend the appropriate dosage for phase Ⅱ trial.Methods:In this trial,totally 23 patients with advanced malignant tumors were enrolled,and divided into two pans,namely single dose and continuous doses.of them,19 patients were divided into 5 single dose groups (0.75,1.5,2.5,3.75 and 5.0 mg·m~(-2)).After taking the initial single doses,the patients received continuous doses(0.5,1.0,1.3,1.5 and 1.8 mg·m~(-2)·d~(-1))for 5 days per week following 7-day washout period.The remaining 4 patients only received a continuous dose of 2.0 mg·m~(-2)·d~(-1).Results:The main adverse effects included gastrointestinal reactions(nausea,vomiting and loss of appetite),fatigue,and bone maiTow suppression.Other observed adverse efleets included diarrhea,fever,dizziness,liver dysfunction and abnormal urine.There was no DLT in single dose study.Considering the single dose therapy is not the way for future clinical use,it was stopped.After continuous dose of 2.0 mg·m~(-2)·d~(-1).the patients experienced the DLT.The MTD in the patients was 1.8 mg·m~(-2)·d~(-1).Efficacy evaluations disclosed 1 patient with PR(5%),8 with SD(40%)and 11 with PD (55%).Conclusion:The therapy of rubitecan is well tolerated in advanced cancer patients.The MTD is 1.8 mg·m~(-2)·d~(-1).Nausea.vomiting and loss of appetite are the most frequent adverse effects.