Sulfatinib, a novel kinase inhibitor, in patients with advanced solid tumors: results from a phase I study.
Sulfatinib is a small molecule kinase inhibitor that targets tumor angiogenesis and immune modulation. This phase I study (NCT02133157) investigated the safety, pharmacokinetic characteristics, and preliminary anti-tumor activity of sulfatinib in patients with advanced solid tumors. The study included a dose-escalation phase (50-350 mg/day, 28-day cycle) with a Fibonacci (3+3) design, and a tumor-specific expansion phase investigating the tumor response to treatment. Two sulfatinib formulations were assessed: formulation 1 (5, 25, and 50 mg capsules) and formulation 2 (50 and 200 mg capsules). Seventy-seven Chinese patients received oral sulfatinib; the maximum tolerated dose was not reached. Dose-limiting toxicities included abnormal hepatic function and coagulation tests, and upper gastrointestinal hemorrhage. The most common treatment-related adverse events were proteinuria, hypertension and diarrhea. Among 34 patients receiving sulfatinib formulation 2, one patient with hepatocellular carcinoma and eight with neuroendocrine tumors exhibited a partial response; 15 had stable disease. The objective response rate was 26.5% (9/34) and the disease control rate was 70.6% (24/34). Pharmacokinetic, safety, and efficacy data supported continuous oral administration of sulfatinib at 300 mg as the recommended phase II dose. Sulfatinib exhibited an acceptable safety profile and encouraging antitumor activity in patients with advanced solid tumors, particularly neuroendocrine tumors.
Department of Gastrointestinal Oncology, The Affiliated Hospital Cancer Center (The 307th Hospital of Chinese People's Liberation Army), Academy of Military Medical Sciences, Beijing, China.
Jian Ming
JM
Xu
Department of Gastrointestinal Oncology, The Affiliated Hospital Cancer Center (The 307th Hospital of Chinese People's Liberation Army), Academy of Military Medical Sciences, Beijing, China.
Yan
Y
Wang
Department of Gastrointestinal Oncology, The Affiliated Hospital Cancer Center (The 307th Hospital of Chinese People's Liberation Army), Academy of Military Medical Sciences, Beijing, China.
Yu Ling
YL
Chen
Department of Gastrointestinal Oncology, The Affiliated Hospital Cancer Center (The 307th Hospital of Chinese People's Liberation Army), Academy of Military Medical Sciences, Beijing, China.
Ru
R
Jia
Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China.
Jie
J
Li
Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China.
Ji Fang
JF
Gong
Clinical and Regulatory Department, Hutchison MediPharma Limited, Shanghai, China.
Jing
J
Li
Clinical and Regulatory Department, Hutchison MediPharma Limited, Shanghai, China.
Chuan
C
Qi
Clinical and Regulatory Department, Hutchison MediPharma Limited, Shanghai, China.
Ye
Y
Hua
Clinical and Regulatory Department, Hutchison MediPharma Limited, Shanghai, China.
Cui Rong
CR
Tan
Drug Metabolism and Pharmacokinetic Department, Hutchison MediPharma Limited, Shanghai, China.
Jian
J
Wang
Drug Metabolism and Pharmacokinetic Department, Hutchison MediPharma Limited, Shanghai, China.
Ke
K
Li
Drug Metabolism and Pharmacokinetic Department, Hutchison MediPharma Limited, Shanghai, China.
Yang
Y
Sai
Oncology Department, Hutchison MediPharma Limited, Shanghai, China.
Feng
F
Zhou
Oncology Department, Hutchison MediPharma Limited, Shanghai, China.
Yong Xin
YX
Ren
Oncology Department, Hutchison MediPharma Limited, Shanghai, China.
Wei Guo
WG
Qing
Chemistry Department, Hutchison MediPharma Limited, Shanghai, China.
Hong
H
Jia
Chemistry Department, Hutchison MediPharma Limited, Shanghai, China.
Wei Guo
WG
Su
Department of Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing, China.
Lin
L
Shen
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012107:Research Design; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
neuroendocrine tumor; phase I clinical trial; solid tumor; sulfatinib; tyrosine kinase inhibitor