title: A Phase I-II dose escalation study of fixed-dose rate gemcitabine, oxaliplatin and capecitabine every two weeks in advanced cholangiocarcinomas.
abstract: BACKGROUND
  Gemcitabine based regimens have been widely used in patients with advanced cholangiocarcinoma (CC), but no standard therapy exists. In this study we aimed to find the maximally tolerated dose (MTD) of a two-week schedule of fixed dose rate (FDR) gemcitabine (G), oxaliplatin (O) and capecitabine (C), and evaluate the safety and efficacy of this regimen in patients with advanced cholangiocarcinoma (CC).
  
  
  METHODS
  In the Phase I part of the study a dose-escalation schedule of FDR G, O and C, administered every two weeks, was performed in patients with solid tumours and no other treatments or advanced CC. In the Phase II part response rate, toxicity, progression-free survival (PFS) and overall survival was evaluated in patients with newly diagnosed advanced CC.
  
  
  RESULTS
  Thirty-six patients entered the Phase I part and G 1 000 mg/m(2) day 1 and 15, O 60 mg/m(2) day 1 and 15, and C 1 000 mg/m(2) BID day 1-7 and day 15-21 were established as MTD. In the Phase II part, 41 patients with advanced CC were included. Overall response rate was 34% and 51% had stable disease, resulting in a clinical benefit rate of 85%. Grade III and IV adverse events were rare. Median survival was 12.5 months (95% CI 9.2-15.9) and median progression-free survival (PFS) was 6.9 months (95% CI 5.1-8.6).
  
  
  CONCLUSIONS
  This outpatient regimen was very feasible with significant activity and a favourable safety profile. Further studies will explore this combination with addition of newer targeted agents.
authors.affiliation: Department of Oncology, The Finsen Centre, Rigshospitalet, Copenhagen, Denmark. ulrik.lassen@rh.regionh.dk
authors.forename: Ulrik
authors.initials: U
authors.lastname: Lassen
authors.forename: Lars Henrik
authors.initials: LH
authors.lastname: Jensen
authors.forename: Morten
authors.initials: M
authors.lastname: Sorensen
authors.forename: Kristoffer S
authors.initials: KS
authors.lastname: Rohrberg
authors.forename: Zaza
authors.initials: Z
authors.lastname: Ujmajuridze
authors.forename: Anders
authors.initials: A
authors.lastname: Jakobsen
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000187:drug effects / Q000473:pathology*; D000069287:Capecitabine; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine