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A phase I trial of PTK787/ZK222584 in combination with pemetrexed and cisplatin in patients with advanced solid tumors.

Authors
  • Sharma, Sunil1
  • Freeman, Burgess
  • Turner, Jeanette
  • Symanowski, James
  • Manno, Phillip
  • Berg, William
  • Vogelzang, Nicholas
  • 1 Nevada Cancer Institute, 1, Breakthrough Way, Las Vegas, NV, 89144, USA. [email protected]
Type
Published Article
Journal
Investigational new drugs
Publication Date
Feb 01, 2009
Volume
27
Issue
1
Pages
63–65
Identifiers
DOI: 10.1007/s10637-008-9157-9
PMID: 18641920
Source
Medline
License
Unknown

Abstract

Angiogenesis is recognized as an important biological process that allows growth of a tumor beyond an initial small size. PTK787/ZK222584, a potent orally active angiogenesis inhibitor capable of inhibiting all known isoforms of Vascular Endothelial Growth Factor (VEGF) receptor, belongs to the class of aminophthalazines. This study investigated a combination of chemotherapy (Cisplatin and Pemetrexed) with PTK787/ZK222584. Eight patients were enrolled but PTK787/ZK222584 dose could not be escalated as planned because of dose limiting toxicities (DLTs) observed on the first dose level. Limited pharmacokinetic profiling of PTK787/ZK222584 revealed no evidence of drug-drug interactions. No responses were seen for this combination. This study was closed secondary to toxicity and lack of efficacy of the designed regimen.

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