title: Phase II study of sorafenib in patients with relapsed or refractory lymphoma.
abstract: 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.
authors.affiliation: Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Guidetti
authors.forename: Carmelo
authors.initials: C
authors.lastname: Carlo-Stella
authors.forename: Silvia L
authors.initials: SL
authors.lastname: Locatelli
authors.forename: Walter
authors.initials: W
authors.lastname: Malorni
authors.forename: Marina
authors.initials: M
authors.lastname: Pierdominici
authors.forename: Cristiana
authors.initials: C
authors.lastname: Barbati
authors.forename: Roberta
authors.initials: R
authors.lastname: Mortarini
authors.forename: Lilli
authors.initials: L
authors.lastname: Devizzi
authors.forename: Paola
authors.initials: P
authors.lastname: Matteucci
authors.forename: Alfonso
authors.initials: A
authors.lastname: Marchianò
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Lanocita
authors.forename: Lucia
authors.initials: L
authors.lastname: Farina
authors.forename: Anna
authors.initials: A
authors.lastname: Dodero
authors.forename: Corrado
authors.initials: C
authors.lastname: Tarella
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Nicola
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.forename: Andrea
authors.initials: A
authors.lastname: Anichini
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Gianni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib