title: Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study.
abstract: BACKGROUND
  CI-994, an oral histone deacetylase inhibitor, has antineoplastic activity and synergism with gemcitabine preclinically. This randomized phase II trial explored whether CI-994 plus gemcitabine improves overall survival, objective response, duration of response, time to treatment failure and change in quality of life (QoL) or pain compared with gemcitabine alone.
  
  
  METHODS
  A total of 174 patients received CG (CI-994 6 mg/m(2)/day days 1-21 plus gemcitabine 1000 mg/m(2) days 1, 8 and 15 each 28-day cycle) or PG (placebo plus gemcitabine 1000 mg/m(2) days 1, 8 and 15 of each 28-day cycle days 1-21).
  
  
  RESULTS
  Median survival was 194 days (CG) versus 214 days (PG) (P = 0.908). The objective response rate with CG was 12% versus 14% with PG when investigator-assessed and 1% versus 6%, respectively, when assessed centrally. Time to treatment failure did not differ between the two arms (P = 0.304). QoL scores at 2 months were worse with CG than with PG. Pain response rates were similar between the two groups. There was an increased incidence of neutropenia and thrombocytopenia with CG.
  
  
  CONCLUSIONS
  Adding CI-994 to gemcitabine in advanced pancreatic carcinoma does not improve overall survival, response rate or time to progression; CG produced decreased QoL and increased hematological toxicity and appears inferior to single-agent gemcitabine.
authors.affiliation: US Oncology Research, Inc., Houston, TX 75702, USA. Donald.Richards@USOncology.com
authors.forename: D A
authors.initials: DA
authors.lastname: Richards
authors.forename: K A
authors.initials: KA
authors.lastname: Boehm
authors.forename: D M
authors.initials: DM
authors.lastname: Waterhouse
authors.forename: D J
authors.initials: DJ
authors.lastname: Wagener
authors.forename: S S
authors.initials: SS
authors.lastname: Krishnamurthi
authors.forename: A
authors.initials: A
authors.lastname: Rosemurgy
authors.forename: W
authors.initials: W
authors.lastname: Grove
authors.forename: K
authors.initials: K
authors.lastname: Macdonald
authors.forename: S
authors.initials: S
authors.lastname: Gulyas
authors.forename: M
authors.initials: M
authors.lastname: Clark
authors.forename: K D
authors.initials: KD
authors.lastname: Dasse
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D010655:Phenylenediamines / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D001549:Benzamides; D010655:Phenylenediamines; D003841:Deoxycytidine; C081895:tacedinaline; D000093542:Gemcitabine