Abstract | UNLABELLED: 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:
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Authors | Nirit Yarom, David Stewart, Rajesh Malik, Julie Wells, Leonard Avruch, Derek J Jonker |
Journal | Current clinical pharmacology
(Curr Clin Pharmacol)
Vol. 8
Issue 1
Pg. 81-8
(Feb 01 2013)
ISSN: 2212-3938 [Electronic] United Arab Emirates |
PMID | 22280327
(Publication Type: Clinical Trial, Phase I, Journal Article)
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Chemical References |
- Antineoplastic Agents
- N-Ac-CHAVC-NH2
- Peptides, Cyclic
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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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