TY - JOUR
T1 - Phase II study of sorafenib in patients with relapsed or refractory lymphoma
AU - Guidetti, Anna
AU - Carlo-Stella, Carmelo
AU - Locatelli, Silvia L.
AU - Malorni, Walter
AU - Pierdominici, Marina
AU - Barbati, Cristiana
AU - Mortarini, Roberta
AU - Devizzi, Lilli
AU - Matteucci, Paola
AU - Marchianò, Alfonso
AU - Lanocita, Rodolfo
AU - Farina, Lucia
AU - Dodero, Anna
AU - Tarella, Corrado
AU - Di Nicola, Massimo
AU - Corradini, Paolo
AU - Anichini, Andrea
AU - Gianni, Alessandro M.
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Lymphoma
KW - Sorafenib
KW - Targeted therapy
KW - Tyrosine kinase inhibitors
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U2 - 10.1111/j.1365-2141.2012.09139.x
DO - 10.1111/j.1365-2141.2012.09139.x
M3 - Article
C2 - 22571717
AN - SCOPUS:84862256588
VL - 158
SP - 108
EP - 119
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 1
ER -