title: Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: A GISCAD randomized phase II study.
abstract: BACKGROUND
  The RAF-MEK-ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations. A phase II randomized trial was designed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer.
  
  
  METHODS
  Locally advanced or metastatic pancreatic adenocarcinoma patients were randomized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400mg bid (arm A) or without sorafenib (arm B).
  
  
  RESULTS
  One hundred and fourteen patients were enrolled; of these, 43 (74.6%) patients progressed in arm A and 44 (82.4%) in arm B. Median progression-free survival was 4.3 months (95% CI: 2.7-6.5) and 4.5 months (95% CI: 2.5-5.2), respectively (HR=0.92; 95% CI: 0.62-1.35). Median overall survival was 7.5 (95% CI: 5.6-9.7) and 8.3 months (95% CI: 6.2-8.7), respectively (HR=0.95; 95% CI: 0.62-1.48). Response rates were 3.4% in arm A and 3.6% in arm B.
  
  
  CONCLUSIONS
  Sorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancer patients, and therefore should not be assessed in phase III trials.
authors.affiliation: Medical Oncology Unit, Università Politecnica delle Marche, Ospedali Riuniti di Ancona, Ancona, Italy. Electronic address: cascinu@yahoo.com.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.affiliation: Medical Oncology Unit, Università Politecnica delle Marche, Ospedali Riuniti di Ancona, Ancona, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.affiliation: Medical Oncology Unit, Ospedale S. Martino, Genova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Sobrero
authors.affiliation: Medical Oncology Unit, Ospedale S. Gerardo, Monza, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bidoli
authors.affiliation: Medical Oncology Unit, Ospedali Riuniti, Bergamo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.affiliation: Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.affiliation: Medical Oncology Unit, Ospedale S. Paolo, Milano, Italy.
authors.forename: Daris
authors.initials: D
authors.lastname: Ferrari
authors.affiliation: Medical Oncology Unit, Treviglio Hospital, Treviglio, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Barni
authors.affiliation: Medical Oncology Unit, C. Poma Hospital, Mantova, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Aitini
authors.affiliation: Medical Oncology Unit, Istituto Oncologico Veneto, Padova, Italy.
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
authors.affiliation: Medical Oncology Unit, Ospedale S. Martino, Genova, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Caprioni
authors.affiliation: Medical Oncology Unit, Ospedale S. Gerardo, Monza, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Villa
authors.affiliation: Medical Oncology Unit, Ospedali Riuniti, Bergamo, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mosconi
authors.affiliation: Medical Oncology Unit, Università Politecnica delle Marche, Ospedali Riuniti di Ancona, Ancona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Faloppi
authors.affiliation: Medical Oncology Unit, University Campus Bio-Medico, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.affiliation: Medical Oncology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Boni
authors.affiliation: Medical Oncology Unit, Policlinico Universitario, Modena, Italy.
authors.forename: Pierfranco
authors.initials: P
authors.lastname: Conte
authors.affiliation: Medical Oncology Unit Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Costanzo
authors.affiliation: New Drug Development Strategies Laboratory, Mario Negri Institute, Milano, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Cinquini
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010671:Phenylurea Compounds / Q000008:administration & dosage; D000077157:Sorafenib; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D010671:Phenylurea Compounds; D003841:Deoxycytidine; D009536:Niacinamide; D000077157:Sorafenib; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Cisplatin; Gemcitabine; Pancreatic cancer; Phase II study; Sorafenib