A phase I/II trial of the oral antiangiogenic agent TSU-68 in patients with advanced hepatocellular carcinoma

被引：75

作者：

Kanai, Fumihiko ^{[1
,2
,3
]}

Yoshida, Haruhiko ^{[2
]}

Tateishi, Ryosuke ^{[2
]}

Sato, Shinpei ^{[2
]}

Kawabe, Takao ^{[2
]}

Obi, Shuntaro ^{[4
]}

Kondo, Yuji ^{[5
]}

Taniguchi, Makoto ^{[5
]}

Tagawa, Kazumi ^{[5
]}

Ikeda, Masafumi ^{[6
]}

Morizane, Chigusa ^{[6
]}

Okusaka, Takuji ^{[6
]}

Arioka, Hitoshi ^{[7
]}

Shiina, Shuichiro ^{[2
]}

Omata, Masao ^{[2
]}

机构：

[1] Chiba Univ Hosp, Dept Gastroenterol, Chuo Ku, Chiba 2608677, Japan

[2] Univ Tokyo, Dept Gastroenterol, Tokyo, Japan

[3] Univ Tokyo, Grad Sch Med, Dept Clin Drug Evaluat, Tokyo, Japan

[4] Kyoundo Hosp, Dept Hepatol, Tokyo, Japan

[5] Mitsui Mem Hosp, Dept Gastroenterol, Tokyo 101, Japan

[6] Natl Canc Ctr, Hepatobiliary & Pancreat Oncol Div, Tokyo, Japan

[7] Yokohama Rosai Hosp, Div Med Oncol, Yokohama, Kanagawa, Japan

来源：

CANCER CHEMOTHERAPY AND PHARMACOLOGY | 2011年 / 67卷 / 02期

关键词：

Advanced HCC; Liver function; TSU-68; Pharmacokinetics; Tolerability; Angiogenesis; TYROSINE KINASE INHIBITOR; E-SELECTIN; CLINICAL-TRIALS; CANCER PATIENTS; SERUM-LEVELS; ANGIOGENESIS; SU6668; MANAGEMENT; SORAFENIB; THERAPIES;

D O I：

10.1007/s00280-010-1320-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

We studied the safety and effectiveness of TSU-68, an oral tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, platelet-derived growth factor receptor and fibroblast growth factor receptor, in patients with advanced hepatocellular carcinoma (HCC). Patients with unresectable or metastatic HCC were eligible for enrollment. In phase I, the safety, tolerability and pharmacokinetics were assessed in patients stratified based on liver function, from no cirrhosis to Child-Pugh class B. The safety and effectiveness were assessed in phase II at the dose determined in phase I. Twelve patients were enrolled in phase I. Dose-limiting toxicities were found with TSU-68 at the dose of 400 mg bid in Child-Pugh B patients, and 200 mg bid was established as the phase II dose. Phase II included 23 additional patients, and the safety and efficacy were evaluated in a total of 35 patients. One patient (2.9%) had a complete response. Two patients (5.7%) had a partial response, and 15 patients (42.8%) showed a stable disease. The median time to progression was 2.1 months, and the median overall survival was 13.1 months. Common adverse events were hypoalbuminemia, diarrhea, anorexia, abdominal pain, malaise, edema and AST/ALT elevation. The analysis of angiogenesis-related parameters suggests that serum-soluble vascular cell adhesion molecule-1 is a possible marker to show the response. TSU-68 at a dose of 200 mg bid determined by stratification into liver function, showed promising preliminary efficacy with a high safety profile in patients with HCC who had been heavily pre-treated.

引用

页码：315 / 324

页数：10

共 32 条

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Clinical significance of serum levels of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in gastric cancer patients [J].