A Phase I Trial to Evaluate the Multiple-Dose Safety and Antitumor Activity of Ursolic Acid Liposomes in Subjects with Advanced Solid Tumors

• Published in: BioMed research international Vol. 2015; no. 2015; pp. 1 - 7
• Main Authors: Wang, Huaqing, Zhou, Shiyong, Zhang, Huilai, Song, Zheng, Wang, Xianhuo, Qian, Zhengzi, Zhao, Jing
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2015; John Wiley & Sons, Inc
• Subjects: Acids; Adolescent; Adult; Aged; Antimitotic agents; Antineoplastic agents; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - adverse effects; Antineoplastic Agents, Phytogenic - pharmacokinetics; Cancer; Cancer therapies; Care and treatment; Clinical Study; Clinical trials; Drug delivery systems; Drug dosages; Drug therapy; FDA approval; Female; Hematology; Hospitals; Humans; Liposomes; Lymphoma; Male; Methods; Middle Aged; Neoplasms - blood; Neoplasms - drug therapy; Neoplasms - mortality; NMR; Nuclear magnetic resonance; Product development; Studies; Triterpenes - administration & dosage; Triterpenes - adverse effects; Triterpenes - pharmacokinetics; Tumors; Urine; Ursolic Acid; China
• ISSN: 2314-6133; 2314-6141; 2314-6141
• DOI: 10.1155/2015/809714

Ursolic acid liposome (UAL), a new antitumor drug, has potential therapeutic value. However, limited clinical data exists regarding multiple-dose safety, antitumor activity, and the recommended dose (RD) of UAL for subjects with advanced solid tumors. All subjects were intravenously administered UAL for 14 consecutive days of a 21-day treatment cycle. Twenty-one subjects were enrolled in 1 of 3 sequential cohorts (56, 74, and 98 mg/m2) to evaluate multiple-dose tolerability and efficacy. Eight additional subjects were treated with UAL (74 mg/m2) to evaluate multiple-dose pharmacokinetics. No ≥grade 3 adverse events (NCI-CTC) were observed. Sixty percent subjects achieved stable disease after 2 treatment cycles. Multiple-dose pharmacokinetic analysis suggested UAL does not accumulate in the body. This trial demonstrates that UAL was tolerable, had manageable toxicity, and could potentially improve patient remission rates. A large phase II study is recommended to confirm these results (i.e., RD of 98 mg/m2).