title: Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma.
abstract: BACKGROUND
  There is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells.
  
  
  OBJECTIVE
  We assessed the activity of sorafenib plus metronomic paclitaxel as second/third-line therapy in advanced ACC patients. We also tested the activity of sorafenib and paclitaxel against NCI-H295R in vitro.
  
  
  METHODS
  Multicenter, prospective phase II trial. Setting Referral centers for ACC.
  
  
  METHODS
  Twenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled. The patients received a combination of i.v. paclitaxel (60 mg/m(2) every week) and oral sorafenib (400 mg twice a day) till progression. The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity.
  
  
  RESULTS
  Tumor progression was observed in nine evaluable patients at the first assessment. These results led to the premature interruption of the trial. The treatment was well tolerated. The most relevant toxicities were fatigue, being grade 2 or 3 in four patients, and hypophosphatemia, being grade 3 in three patients. In the in vitro study, sorafenib impaired the viability of H295R cells with dose-response and time-response relationships. The in vitro sorafenib activity was not increased in combination with paclitaxel.
  
  
  CONCLUSIONS
  Despite the in vitro activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended.
authors.affiliation: Department of Clinical and Biological Science, University of Turin, Azienda Ospedaliero Universitaria San Luigi, Regione Gonzole 10, 10043 Orbassano, Italy. alfredo.berruti@gmail.com
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.forename: Paola
authors.initials: P
authors.lastname: Sperone
authors.forename: Anna
authors.initials: A
authors.lastname: Ferrero
authors.forename: Antonina
authors.initials: A
authors.lastname: Germano
authors.forename: Arianna
authors.initials: A
authors.lastname: Ardito
authors.forename: Adriano Massimiliano
authors.initials: AM
authors.lastname: Priola
authors.forename: Silvia
authors.initials: S
authors.lastname: De Francia
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.forename: Fulvia
authors.initials: F
authors.lastname: Daffara
authors.forename: Daniele
authors.initials: D
authors.lastname: Generali
authors.forename: Sophie
authors.initials: S
authors.lastname: Leboulleux
authors.forename: Paola
authors.initials: P
authors.lastname: Perotti
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001557:Benzenesulfonates / Q000008:administration & dosage; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D017239:Paclitaxel / Q000008:administration & dosage; D010671:Phenylurea Compounds; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage; D000077157:Sorafenib
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D017239:Paclitaxel