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

AbstractPURPOSE: METHODS:
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.
RESULTS:
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.
CONCLUSIONS:
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.
AuthorsFumihiko Kanai, Haruhiko Yoshida, Ryosuke Tateishi, Shinpei Sato, Takao Kawabe, Shuntaro Obi, Yuji Kondo, Makoto Taniguchi, Kazumi Tagawa, Masafumi Ikeda, Chigusa Morizane, Takuji Okusaka, Hitoshi Arioka, Shuichiro Shiina, Masao Omata
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 67 Issue 2 Pg. 315-24 (Feb 2011) ISSN: 1432-0843 [Electronic] Germany
PMID20390419 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiogenesis Inhibitors
  • Angiogenesis Modulating Agents
  • Biomarkers
  • Indoles
  • Oxindoles
  • Propionates
  • Pyrroles
  • Vascular Cell Adhesion Molecule-1
  • orantinib
Topics
  • Administration, Oral
  • Aged
  • Angiogenesis Inhibitors (pharmacology, therapeutic use, toxicity)
  • Angiogenesis Modulating Agents (blood)
  • Area Under Curve
  • Biomarkers (blood)
  • Carcinoma, Hepatocellular (blood, drug therapy, pathology)
  • Female
  • Humans
  • Indoles (pharmacology, therapeutic use, toxicity)
  • Liver Neoplasms (blood, drug therapy, pathology)
  • Male
  • Middle Aged
  • Necrosis (chemically induced)
  • Oxindoles
  • Propionates (pharmacology, therapeutic use, toxicity)
  • Pyrroles
  • Survival Analysis
  • Treatment Outcome
  • Vascular Cell Adhesion Molecule-1 (blood)

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