A phase I trial to evaluate the multiple-dose safety and antitumor activity of ursolic acid liposomes in subjects with advanced solid tumors

Biomed Res Int. 2015:2015:809714. doi: 10.1155/2015/809714. Epub 2015 Mar 19.

Abstract

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/m(2)) to evaluate multiple-dose tolerability and efficacy. Eight additional subjects were treated with UAL (74 mg/m(2)) 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/m(2)).

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / drug therapy*
  • Neoplasms / mortality
  • Triterpenes / administration & dosage*
  • Triterpenes / adverse effects
  • Triterpenes / pharmacokinetics*
  • Ursolic Acid

Substances

  • Antineoplastic Agents, Phytogenic
  • Triterpenes