title: Phase I clinical trial of continuous infusion of tyroserleutide in patients with advanced hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is usually diagnosed in advanced stage, which causes difficulty of using surgical treatment. Previous studies demonstrated that tyroserleutide (YSL), an immunologically active tripeptide compound, could suppress the proliferation and tumor formation of some liver cancer cell lines. We aimed to investigate the feasibility and toxicity of continuous administration of YSL by a portable infusion pump to patients with advanced HCC and its biologically effective but non-toxic doses used in outpatient setting. Forty patients (12 in stage 1, 28 in stage 2, total 10 treated in each dose cohort) were treated with YSL 6, 12, 18, or 24 mg/day lasting for 5 days. No treatment-related mortality was observed. The overall response rates were 25% (3/12) and 7.2% (2/28) in stages 1 and 2, respectively. The median 6-month overall survival (OS) in stage 1 was 75, 64, and 41 days for 6, 18, and 24 mg/day groups, respectively; all patients survived in the 12 mg/day group. The median OS in stage 2 was 68, 72, and 60 days for 12, 18, and 24 mg/day groups, respectively; all survived in the 6 mg/day group. The most common adverse reactions were abnormal liver function (59/107) and hemogram (22/107). The dose-limiting toxicities of 24 mg/day group contained abdominal distention (1/10), sicchasia (1/10), hyponatremia (1/10), myocardiac ischemia (1/10), and abnormal hemogram (6/10). We conclude that the continuous administration of YSL by portable infusion pump was well tolerated. Treatment responses of doses 6 and 12 mg/day were better than other two groups. Further studies of continuous infusion of YSL to determine its efficacy are warranted.
authors: Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Road, Wuhan, Hubei 430030, China.
authors: Zhen-Yu
authors: ZY
authors: Xiao
authors: Jin-Bin
authors: JB
authors: Jia
authors: Lin
authors: L
authors: Chen
authors: Wei
authors: W
authors: Zou
authors: Xiao-Ping
authors: XP
authors: Chen
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; C484773:H-Tyr-Ser-Leu-OH