title: Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate.
abstract: OBJECTIVE
  This phase III, randomized, open-label, multicenter study compared the overall survival associated with irinotecan plus gemcitabine (IRINOGEM) versus gemcitabine monotherapy (GEM) in patients with chemotherapy-naive, locally advanced or metastatic pancreatic cancer.
  
  
  METHODS
  IRINOGEM patients received starting doses of gemcitabine 1,000 mg/m2 and irinotecan 100 mg/m2 given weekly for 2 weeks every 3-week cycle. GEM patients received gemcitabine 1,000 mg/m2 weekly for 7 of 8 weeks (induction) and then weekly for 3 of 4 weeks. The primary end point of the trial was survival. Secondary end points included tumor response, time to tumor progression (TTP), changes in CA 19-9, and safety.
  
  
  RESULTS
  In each arm, 180 randomly assigned patients comprised the intent-to-treat population evaluated for efficacy; 173 IRINOGEM and 169 GEM patients were treated. Median survival times were 6.3 months for IRINOGEM (95% CI, 4.7 to 7.5 months) and 6.6 months for GEM (95% CI, 5.2 to 7.8 months; log-rank P =.789). Tumor response rates were 16.1% (95% CI, 11.1% to 22.3%) for IRINOGEM and 4.4% (95% CI, 1.9% to 8.6%) for GEM (chi2 P <.001). Median TTP was 3.5 months for IRINOGEM versus 3.0 months for GEM (log-rank P =.352). However, subset analyses in patients with locally advanced disease suggested a TTP advantage with IRINOGEM versus GEM (median, 7.7 v 3.9 months). CA 19-9 progression was positively correlated with tumor progression. The incidence of grade 3 diarrhea was higher in the IRINOGEM group but grade 3 to 4 hematologic toxicities and quality-of-life outcomes were similar.
  
  
  CONCLUSIONS
  IRINOGEM safely improved the tumor response rate compared with GEM but did not alter overall survival.
authors.affiliation: University of Miami and Sylvester Cancer Center, Miami, FL 33162, USA. crocha@med.miami.edu
authors.forename: Caio M
authors.initials: CM
authors.lastname: Rocha Lima
authors.forename: Mark R
authors.initials: MR
authors.lastname: Green
authors.forename: Robert
authors.initials: R
authors.lastname: Rotche
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Miller
authors.forename: G Mark
authors.initials: GM
authors.lastname: Jeffrey
authors.forename: Laura A
authors.initials: LA
authors.lastname: Cisar
authors.forename: Adele
authors.initials: A
authors.lastname: Morganti
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Orlando
authors.forename: Gabriela
authors.initials: G
authors.lastname: Gruia
authors.forename: Langdon L
authors.initials: LL
authors.lastname: Miller
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011788:Quality of Life; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine