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

• Published in: Leukemia & lymphoma Vol. 54; no. 12; pp. 2627 - 2630
• Main Authors: Brander, Danielle, Rizzieri, David, Gockerman, Jon, Diehl, Louis, Shea, Thomas Charles, Decastro, Carlos, Moore, Joseph O., Beaven, Anne
• Format: Journal Article
• Language: English
• Published: United States Informa Healthcare 01.12.2013; Taylor & Francis
• Subjects: Administration, Oral; Adult; Aged; Aged, 80 and over; angiogenesis; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; diffuse large B-cell lymphoma; Female; Humans; Lymphoma, Large B-Cell, Diffuse - drug therapy; Male; Middle Aged; Phthalazines - administration & dosage; Phthalazines - adverse effects; Phthalazines - therapeutic use; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; PTK787/ZK222584; Pyridines - administration & dosage; Pyridines - adverse effects; Pyridines - therapeutic use; Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors; Recurrence; Remission Induction; Treatment Outcome; vatalanib
• ISSN: 1042-8194; 1029-2403; 1029-2403
• DOI: 10.3109/10428194.2013.784969

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.