title: Could interferon still play a role in metastatic renal cell carcinoma? A randomized study of two schedules of sorafenib plus interferon-alpha 2a (RAPSODY).
abstract: BACKGROUND
  Sorafenib has proven efficacy in metastatic renal cell carcinoma (mRCC). Interferon (IFN) has antiangiogenic activity that is thought to be both dose- and administration-schedule dependent.
  
  
  OBJECTIVE
  To compare two different schedules of IFN combined with sorafenib.
  
  
  METHODS
  Single-stage, prospective, noncomparative, randomized, open-label, multicenter, phase 2 study on previously untreated patients with mRCC and Eastern Cooperative Oncology Group performance status 0-2.
  
  
  METHODS
  Sorafenib 400mg twice daily plus subcutaneous IFN, 9 million units (MU) three times a week (Arm A) or 3 MU five times a week (Arm B).
  
  
  METHODS
  Primary end points were progression-free survival (PFS) for each arm and safety. Data were evaluated according to an intent-to-treat analysis.
  
  
  CONCLUSIONS
  A total of 101 patients were evaluated. Median PFS was 7.9 mo in Arm A and 8.6 mo in Arm B (p=0.049) and the median duration of response was 8.5 and 19.2 mo, respectively (p=0.0013). Nine partial responses were observed in Arm A, and three complete and 14 partial responses were observed in Arm B (17.6% vs 34.0%; p=0.058); 24 and 21 patients (47% and 42%), respectively, achieved stable disease. The most common grade 3-4 toxicities were fatigue plus asthenia (28% vs 16%; p=0.32) and hand-foot skin reactions (20% vs 18%).
  
  
  CONCLUSIONS
  Sorafenib plus frequent low-dose IFN showed good efficacy and tolerability. Further investigations should be warranted to identify a possible positioning of this intriguing regimen (6% complete response rate) in the treatment scenario of mRCC.
authors.affiliation: Azienda USL8, Arezzo, Italy. sergio.bracarda@usl8.toscana.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Bracarda
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Corrado
authors.initials: C
authors.lastname: Boni
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Claudia
authors.initials: C
authors.lastname: Mucciarini
authors.forename: Antonio
authors.initials: A
authors.lastname: Pazzola
authors.forename: Enrico
authors.initials: E
authors.lastname: Cortesi
authors.forename: Donatello
authors.initials: D
authors.lastname: Gasparro
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Costanzo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.forename: Michela
authors.initials: M
authors.lastname: Cinquini
authors.forename: Claudia
authors.initials: C
authors.lastname: Caserta
authors.forename: Chiara
authors.initials: C
authors.lastname: Paglino
authors.forename: Verena
authors.initials: V
authors.lastname: De Angelis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010671:Phenylurea Compounds; D011994:Recombinant Proteins; D009536:Niacinamide; D000077157:Sorafenib