title: Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study.
abstract: OBJECTIVE
  Single-agent gemcitabine became standard first-line treatment for advanced pancreatic cancer after demonstration of superiority compared with fluorouracil. The Gruppo Italiano Pancreas 1 randomized phase III trial aimed to compare gemcitabine plus cisplatin versus gemcitabine alone (ClinicalTrials.gov ID NCT00813696).
  
  
  METHODS
  Patients with locally advanced or metastatic pancreatic cancer, age 18 to 75 years, and Karnofsky performance status (KPS) > or = 50, were randomly assigned to receive gemcitabine (arm A) or gemcitabine plus cisplatin (arm B). Arm A: gemcitabine 1,000 mg/m(2) weekly for 7 weeks, and, after a 1-week rest, on days 1, 8, and 15 every 4 weeks. Arm B: cisplatin 25 mg/m(2) added weekly to gemcitabine, except cycle 1 day 22. Primary end point was overall survival. To have 8% power of detecting a 0.74 hazard ratio (HR) of death, with bilateral alpha .05, 355 events were needed and 400 patients planned.
  
  
  RESULTS
  Four hundred patients were enrolled (arm A: 199; arm B: 201). Median age was 63, 59% were male, 84% had stage IV, and 83% had KPS > or = 80. Median overall survival was 8.3 months versus 7.2 months in arm A and B, respectively (HR, 1.10; 95% CI, 0.89 to 1.35; P = .38). Median progression-free survival was 3.9 months versus 3.8 months in arm A and B, respectively (HR, 0.97; 95% CI, 0.80 to 1.19; P = .80). The objective response rate was 10.1% in A and 12.9% in B (P = .37). Clinical benefit was experienced by 23.0% in A and 15.1% in B (P = .057). Combination therapy produced more hematologic toxicity, without relevant differences in nonhematologic toxicity.
  
  
  CONCLUSIONS
  The addition of weekly cisplatin to gemcitabine failed to demonstrate any improvement as first-line treatment of advanced pancreatic cancer.
authors.affiliation: Medical and Experimental Oncology Unit, Oncology Institute Giovanni Paolo II, Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colucci
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Costanzo
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Giacomo
authors.initials: G
authors.lastname: Cartenì
authors.forename: Bruno
authors.initials: B
authors.lastname: Massidda
authors.forename: Elisa
authors.initials: E
authors.lastname: Dapretto
authors.forename: Luigi
authors.initials: L
authors.lastname: Manzione
authors.forename: Elena
authors.initials: E
authors.lastname: Piazza
authors.forename: Mirella
authors.initials: M
authors.lastname: Sannicolò
authors.forename: Marco
authors.initials: M
authors.lastname: Ciaparrone
authors.forename: Luigi
authors.initials: L
authors.lastname: Cavanna
authors.forename: Francesco
authors.initials: F
authors.lastname: Giuliani
authors.forename: Evaristo
authors.initials: E
authors.lastname: Maiello
authors.forename: Antonio
authors.initials: A
authors.lastname: Testa
authors.forename: Paolo
authors.initials: P
authors.lastname: Pederzoli
authors.forename: Massimo
authors.initials: M
authors.lastname: Falconi
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine