Objective:This study evaluated the safety and preliminary efficacy of vorolanib,a novel tyrosine kinase inhibitor,for treatment of patients with advanced solid tumors.Methods:During dose escalation,patients received i...Objective:This study evaluated the safety and preliminary efficacy of vorolanib,a novel tyrosine kinase inhibitor,for treatment of patients with advanced solid tumors.Methods:During dose escalation,patients received increasing doses of oral vorolanib(50-250 mg once daily)in cycles of four weeks for up to one year.During dose expansion,patients received recommended doses(100 and 200 mg)in 4-week cycles.The primary endpoint was to determine the safety and maximum tolerated dose and/or the recommended phase II dose(RP2 D).The severity and type of adverse drug reactions(ADRs)were assessed using the Common Terminology Criteria for Adverse Events version 4.0.The second endpoint was preliminary efficacy in terms of objective response and progression-free survival(PFS).Results:No dose-limiting toxicity occurred during dose escalation(50-250 mg).Five(26.3%)patients in the escalation cohort(n=19)and 12(48.0%)in the expansion cohort(n=25)experienced grade 3 ADRs.The most common ADRs were hair color changes,fatigue,portal hypertension,hypertriglyceridemia,and proteinuria.During dose expansion,the patients treated with 200 mg and 100 mg(once daily)showed an objective response rate of 22.2%and 5.9%,respectively;the disease control rate was 88.9%and 73.3%,respectively;the median PFS was9.9[95%confidence interval(95%CI):7.4-not reached]months and 3.8(95%CI:1.9-not reached)months,respectively.Conclusions:Oral vorolanib at a dose of 200 mg(once daily)exhibited an acceptable safety profile and favorable clinical benefit for patients with advanced solid tumors.The RP2 D for vorolanib was determined to be 200 mg as a daily regimen.展开更多
Two hundred and thirty-six patinets with various advanced malignant solid tumors treated by combined chemotherapy with routine doses of cisplatin (DDP) from 1980 to 1986 are presented. According to different doses of ...Two hundred and thirty-six patinets with various advanced malignant solid tumors treated by combined chemotherapy with routine doses of cisplatin (DDP) from 1980 to 1986 are presented. According to different doses of cisplatin everyday, the patients were divided into 4 groups: (1) 20 ing/day×4- 5, 80 cases; (2) 30 mg day × 3 - 5, 91 cases; (3) 40 mg/ day 3 -4, 37 cases; (4) 50 mg/day×2 - 3, 28 cases. Each group was repeated for 3 weeks. The effect and toxicity were analysed and compared with 22 cases treated by single DDP in 1975. The response (CR+PR) rate was 39.2% in 194 evaluated patients. The response rate was similar in group 20 mg and single DDP (29.2% and 27.3%). Ths response rate was lower than that of group 30 mg, 40 mg, and 50 mg 43.4% and 50%) (P<0.05). The remissions in various groups were not significantly different.The toxicity of combined chemotherapy was not severe. 91.1% of patients had nausea and vomiting. There was no statistical difference in the various groups. Bone marrow suppresion was less in single DDP group than that of combined chemotherapy group (P<0.05), DDP 30-50 mg 1/d×5-3 was better than HD-DDP in some patients.展开更多
文摘Objective:This study evaluated the safety and preliminary efficacy of vorolanib,a novel tyrosine kinase inhibitor,for treatment of patients with advanced solid tumors.Methods:During dose escalation,patients received increasing doses of oral vorolanib(50-250 mg once daily)in cycles of four weeks for up to one year.During dose expansion,patients received recommended doses(100 and 200 mg)in 4-week cycles.The primary endpoint was to determine the safety and maximum tolerated dose and/or the recommended phase II dose(RP2 D).The severity and type of adverse drug reactions(ADRs)were assessed using the Common Terminology Criteria for Adverse Events version 4.0.The second endpoint was preliminary efficacy in terms of objective response and progression-free survival(PFS).Results:No dose-limiting toxicity occurred during dose escalation(50-250 mg).Five(26.3%)patients in the escalation cohort(n=19)and 12(48.0%)in the expansion cohort(n=25)experienced grade 3 ADRs.The most common ADRs were hair color changes,fatigue,portal hypertension,hypertriglyceridemia,and proteinuria.During dose expansion,the patients treated with 200 mg and 100 mg(once daily)showed an objective response rate of 22.2%and 5.9%,respectively;the disease control rate was 88.9%and 73.3%,respectively;the median PFS was9.9[95%confidence interval(95%CI):7.4-not reached]months and 3.8(95%CI:1.9-not reached)months,respectively.Conclusions:Oral vorolanib at a dose of 200 mg(once daily)exhibited an acceptable safety profile and favorable clinical benefit for patients with advanced solid tumors.The RP2 D for vorolanib was determined to be 200 mg as a daily regimen.
文摘Two hundred and thirty-six patinets with various advanced malignant solid tumors treated by combined chemotherapy with routine doses of cisplatin (DDP) from 1980 to 1986 are presented. According to different doses of cisplatin everyday, the patients were divided into 4 groups: (1) 20 ing/day×4- 5, 80 cases; (2) 30 mg day × 3 - 5, 91 cases; (3) 40 mg/ day 3 -4, 37 cases; (4) 50 mg/day×2 - 3, 28 cases. Each group was repeated for 3 weeks. The effect and toxicity were analysed and compared with 22 cases treated by single DDP in 1975. The response (CR+PR) rate was 39.2% in 194 evaluated patients. The response rate was similar in group 20 mg and single DDP (29.2% and 27.3%). Ths response rate was lower than that of group 30 mg, 40 mg, and 50 mg 43.4% and 50%) (P<0.05). The remissions in various groups were not significantly different.The toxicity of combined chemotherapy was not severe. 91.1% of patients had nausea and vomiting. There was no statistical difference in the various groups. Bone marrow suppresion was less in single DDP group than that of combined chemotherapy group (P<0.05), DDP 30-50 mg 1/d×5-3 was better than HD-DDP in some patients.
