PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor of vascular endothelial growth factor (VEGF), has modest activity in myelofibrosis with myeloid metaplasia.
Angiogenesis is part of the pathophysiology of myelofibrosis with myeloid metaplasia (MMM). PTK787/ZK 222584 (PTK/ZK) is a novel inhibitor of vascular endothelial growth factor receptors. Twenty-nine patients with MMM received a continuous dosing schedule of PTK/ZK doses of 500 or 750 mg twice daily (BID). Transient potentially PTK/ZK related mild nausea, vomiting, dizziness, fatigue, thrombocytopenia, or anorexia occurred in 15% of patients. Dose limiting toxicities of dyspepsia, proteinurea, and/or mucositis were observed in patients treated with 750 mg BID. One (3%) and five (17%) patients achieved complete remission and clinical improvement, respectively. PTK/ZK has modest activity in patients with MMM.
Giles
Francis J
FJ
The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030, USA. frankgiles@aol.com
List
Alan F
AF
Carroll
Michael
M
Cortes
Jorge E
JE
Valickas
Joyce
J
Chen
Bee-Lian
BL
Masson
Eric
E
Jacques
Christian
C
Laurent
Dirk
D
Albitar
Maher
M
Feldman
Eric J
EJ
Roboz
Gail J
GJ
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010793:Phthalazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D010793:Phthalazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C404768:vatalanib