Phase II study of sorafenib in patients with relapsed or refractory lymphoma

• Published in: British journal of haematology Vol. 158; no. 1; pp. 108 - 119
• Main Authors: Guidetti, Anna, Carlo-Stella, Carmelo, Locatelli, Silvia L., Malorni, Walter, Pierdominici, Marina, Barbati, Cristiana, Mortarini, Roberta, Devizzi, Lilli, Matteucci, Paola, Marchianò, Alfonso, Lanocita, Rodolfo, Farina, Lucia, Dodero, Anna, Tarella, Corrado, Di Nicola, Massimo, Corradini, Paolo, Anichini, Andrea, Gianni, Alessandro M.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01-07-2012; Blackwell
• Subjects: Adolescent; Adult; Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Benzenesulfonates - adverse effects; Benzenesulfonates - therapeutic use; Biological and medical sciences; biomarkers; Biomarkers, Tumor - blood; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; lymphoma; Lymphoma - blood; Lymphoma - drug therapy; Male; Medical sciences; Middle Aged; Niacinamide - analogs & derivatives; Phenylurea Compounds; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyridines - adverse effects; Pyridines - therapeutic use; sorafenib; targeted therapy; tyrosine kinase inhibitors; Young Adult; Antineoplastic agent; Human; Relapse; Treatment resistance; Hematology; Tyrosine kinase inhibitor; Targeted therapy; biomarkers; Enzyme inhibitor; Biological marker; Malignant hemopathy; Lymphoid neoplasm; Lymphoma; tyrosine kinase inhibitors; Treatment; Lymphoproliferative syndrome; Sorafenib; Phase II trial; Multikinase inhibitor; Antiangiogenic agent; Cancer
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2012.09139.x

Summary
The safety and activity of the multikinase inhibitor sorafenib were investigated in patients with relapsed or refractory lymphoproliferative disorders who received sorafenib (400 mg) twice daily until disease progression or appearance of significant clinical toxicity. The primary endpoint was overall response rate (ORR). Biomarkers of sorafenib activity were analysed at baseline and during treatment. Thirty patients (median age, 61 years; range, 18–74) received a median of 4 months of therapy. Grade 3–4 toxicities included hand/foot skin reactions (20%), infections (12%), neutropenia (20%) and thrombocytopenia (14%). Two patients achieved complete remission (CR), and two achieved partial remission (PR) for an ORR of 13%. Stable disease (SD) and progressive disease (PD) was observed in 15 (50%) and 11 patients (37%), respectively. The median overall survival (OS) for all patients was 16 months. For patients who achieved CR, PR and SD, the median time to progression and OS was 5 and 24 months, respectively. Compared with patients with PD, responsive patients had significantly higher baseline levels of extracellular signal‐regulated kinase phosphorylation and autophagy and presented a significant reduction of these parameters after 1 month of therapy. Sorafenib was well tolerated and had a clinical activity that warrants development of combination regimens.