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Phase I clinical trial of Exherin (ADH-1) in patients with advanced solid tumors.

AbstractUNLABELLED:
ADH-1 (Exherin™) is a pentapeptide, which competitively inhibits N-cadherin, resulting in vascular disruptive effect of tumor vasculature in preclinical models. This study was designed to assess the toxicity of ADH-1 and to determine the maximal tolerated dose (MTD).
PATIENTS AND METHODS:
Adult patients with advanced measurable solid tumors were stratified according to their tumor N-cadherin status. ADH-1 was administered as a short infusion, every six weeks. Assessment of response was done every 6 weeks. PK parameters included: estimated volume of distribution of the central compartment, the α and β phase half-lives, area under the plasma concentration- time curve (AUC), clearance, and volume of distribution. Target lesions were assessed by dynamic contrast enhancing- magnetic resonance imaging (DCE-MRI).
RESULTS:
46 patients were enrolled, 25 (54%) had N-cadherin positive status. The doses administered ranged from 50 mg/m2 to 1000 mg/m2, and the MTD was not reached. The PK analysis of the concentration-time data displayed a biphasic profile. Most of the toxicities were grade 1 and 2 with fatigue, nausea, chest pain and dysgeusia being the most common. Eleven patients had disease control, the single patient who had partial response had N-cadherin positive tumor.
CONCLUSION:
ADH-1 is a well tolerated drug with a modest anti tumor effect in tumors which express N-cadherin.
AuthorsNirit Yarom, David Stewart, Rajesh Malik, Julie Wells, Leonard Avruch, Derek J Jonker
JournalCurrent clinical pharmacology (Curr Clin Pharmacol) Vol. 8 Issue 1 Pg. 81-8 (Feb 01 2013) ISSN: 2212-3938 [Electronic] United Arab Emirates
PMID22280327 (Publication Type: Clinical Trial, Phase I, Journal Article)
Chemical References
  • Antineoplastic Agents
  • N-Ac-CHAVC-NH2
  • Peptides, Cyclic
Topics
  • Adult
  • Aged
  • Antineoplastic Agents (therapeutic use)
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms (drug therapy)
  • Peptides, Cyclic (adverse effects, pharmacokinetics, therapeutic use)

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