Vatalanib: the clinical development of a tyrosine kinase inhibitor of angiogenesis in solid tumours.
The licensing of bevacizumab in patients with metastatic colorectal cancer has fueled research in angiogenesis. Vatalanib (PTK787/ZK 222584), a potent oral tyrosine kinase inhibitor with a selective range of molecular targets, has been extensively investigated and has shown promising results in patients with colorectal cancer in early trials. Dynamic contrast-enhanced MRI has been useful as a pharmacodynamic tool to define the dose that has a biological effect. The primary objectives of the Phase III CONFIRM (Colorectal Oral Novel Therapy for the Inhibition of Angiogenesis and Retarding of Metastases in First-line) studies were not met. However, an interesting pre-planned subset analysis in both studies showed that patients with high lactate dehydrogenase derived clinical benefit. Although this type of analysis should always be considered with caution, the Phase III clinical programme of vatalanib is continuing with further innovative studies looking at other indications and schedules for vatalanib.
Scott
Edwina N
EN
University of Leicester, Department of Cancer Studies and Molecular Medicine, Leicester, LE1 5WW, UK.
Meinhardt
Gerold
G
Jacques
Christian
C
Laurent
Dirk
D
Thomas
Anne L
AL
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010793:Phthalazines / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D010793:Phthalazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C404768:vatalanib; D011505:Protein-Tyrosine Kinases