title: Phase II open label study of the oral vascular endothelial growth factor-receptor inhibitor PTK787/ZK222584 (vatalanib) in adult patients with refractory or relapsed diffuse large B-cell lymphoma.
abstract: PTK787/ZK222584 (vatalanib), an orally active inhibitor of vascular endothelial growth factor receptors (VEGFRs), was evaluated in this phase II study of 20 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received once-daily PTK787/ZK222584 at a target dose of 1250 mg. Eighteen patients were evaluable for response: one patient had a complete response (CR), six patients had stable disease but subsequently progressed, 10 patients had progressive disease by three cycles and one subject withdrew before response evaluation. The patient who attained a CR underwent autologous stem cell transplant and remains disease-free 76 months after study completion. There were no grade 4 toxicities. Grade 3 thrombocytopenia occurred in 20% and grade 3 hypertension occurred in 10%. There were no episodes of grade 3 proteinuria. In conclusion, PTK787/ZK222584 was well tolerated in a heavily pretreated population of patients with DLBCL, although its therapeutic potential as a single agent in DLBCL appears limited.
authors.affiliation: Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke Cancer Institute , Durham, NC , USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Brander
authors.forename: David
authors.initials: D
authors.lastname: Rizzieri
authors.forename: Jon
authors.initials: J
authors.lastname: Gockerman
authors.forename: Louis
authors.initials: L
authors.lastname: Diehl
authors.forename: Thomas Charles
authors.initials: TC
authors.lastname: Shea
authors.forename: Carlos
authors.initials: C
authors.lastname: Decastro
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.forename: Anne
authors.initials: A
authors.lastname: Beaven
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010793:Phthalazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010793:Phthalazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C404768:vatalanib; D040262:Receptors, Vascular Endothelial Growth Factor