title: TOKIO rationale and protocol: a phase II study to evaluate the activity and safety of third-line tyrosine kinase inhibitor after 2 tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  The introduction of agents targeting vascular endothelial growth factor has radically changed the approach to metastatic renal cell carcinoma (mRCC): sunitinib and pazopanib are now the standard first-line therapy in mRCC. At sunitinib failure, second-line axitinib or everolimus or sorafenib should be considered to improve the clinical outcome. No data are available for a third-line tyrosine kinase inhibitor (TKI) after 2 previous lines of therapy with TKIs. At pazopanib failure, no prospective data are available.
  
  
  METHODS
  The TOKIO study was designed to evaluate progression-free survival, safety, and efficacy of third-line therapy with TKI in 44 patients already treated with 2 previous lines of TKIs in 10 Italian centers, and relapsed from sunitinib-axitinib (group A) or pazopanib-sorafenib (group B). Standard treatment is sorafenib in group A and sunitinib in group B, administered until disease progression or unacceptable toxicity. Secondary endpoints include the evaluation of overall survival, safety, and quality of life.
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Verzoni
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grassi
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Montone
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Galli
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Necchi
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan - Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procopio
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D000068338:Everolimus / Q000008:administration & dosage; D007093:Imidazoles / Q000008:administration & dosage; D007191:Indazoles / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D011788:Quality of Life; D000077157:Sorafenib; D013449:Sulfonamides / Q000008:administration & dosage; D000077210:Sunitinib; D016896:Treatment Outcome; D053634:TYK2 Kinase / Q000037:antagonists & inhibitors; D012107:Research Design
chemical_list: D000970:Antineoplastic Agents; D000077784:Axitinib; D000068338:Everolimus; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D009536:Niacinamide; C516667:pazopanib; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D000077157:Sorafenib; D013449:Sulfonamides; D000077210:Sunitinib; D053634:TYK2 Kinase