title: PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor of vascular endothelial growth factor (VEGF), has modest activity in myelofibrosis with myeloid metaplasia.
abstract: 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.
authors.affiliation: The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 428, Houston, TX 77030, USA. frankgiles@aol.com
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Alan F
authors.initials: AF
authors.lastname: List
authors.forename: Michael
authors.initials: M
authors.lastname: Carroll
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Joyce
authors.initials: J
authors.lastname: Valickas
authors.forename: Bee-Lian
authors.initials: BL
authors.lastname: Chen
authors.forename: Eric
authors.initials: E
authors.lastname: Masson
authors.forename: Christian
authors.initials: C
authors.lastname: Jacques
authors.forename: Dirk
authors.initials: D
authors.lastname: Laurent
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Feldman
authors.forename: Gail J
authors.initials: GJ
authors.lastname: Roboz
mesh_terms: 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*
chemical_list: D010793:Phthalazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C404768:vatalanib