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: ADH-1 is a well tolerated drug with a modest anti tumor effect in tumors which express N-cadherin.
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 tumorN-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.
Authors: Rhonda L Bitting; Daneen Schaeffer; Jason A Somarelli; Mariano A Garcia-Blanco; Andrew J Armstrong Journal: Cancer Metastasis Rev Date: 2014-09 Impact factor: 9.264
Authors: Felix Bremmer; Simon Schallenberg; Hubertus Jarry; Stefan Küffer; Silke Kaulfuss; Peter Burfeind; Arne Strauß; Paul Thelen; Heinz Joachim Radzun; Philipp Ströbel; Friedemann Honecker; Carl Ludwig Behnes Journal: Oncotarget Date: 2015-10-20
Authors: Krzysztof Marek Mrozik; Orest William Blaschuk; Chee Man Cheong; Andrew Christopher William Zannettino; Kate Vandyke Journal: BMC Cancer Date: 2018-10-01 Impact factor: 4.430