title: Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: a phase II study of the Belgian Group of Digestive Oncology.
abstract: BACKGROUND
  Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression.
  
  
  METHODS
  In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m(2) at week 1, then 250 mg/m(2)/week) and Gemcitabine (1 g/m(2) on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin toxic effect on efficacy.
  
  
  RESULTS
  Forty-four patients (41% locally advanced/59% metastatic) were enrolled. Median age was 61.5 years; ECOG PS was 0 (68%) or 1. Six months PFS reached 47%. Median OS was 13.5 months [95% confidence interval (CI) 9.8-31.8 months]. Nine patients (20.4%) had PR and disease-control rate was 79.5%. Grade 3/4-related toxic effects were haematological (52.2%), skin rash (13.6%) and fatigue (11.4%). KRAS mutations were found in 7 of 27 patients and had no influence on PFS. Skin toxic effect ≥grade 2 was associated with increased PFS (P = 0.05).
  
  
  CONCLUSIONS
  Our study met its primary end point, suggesting that Gemcitabine-Cetuximab has activity in cholangiocarcinoma. KRAS status was not associated with PFS, unlike skin toxic effect, which could be used as a surrogate marker for efficacy. ClinicalTrials.gov Identifier: NCT00747097.
authors: Hepato-Gastroenterology Unit, Cliniques Universitaires Saint-Luc Bruxelles, Bruxelles.
authors: I
authors: I
authors: Borbath
authors: A
authors: A
authors: Ceratti
authors: C
authors: C
authors: Verslype
authors: A
authors: A
authors: Demols
authors: T
authors: T
authors: Delaunoit
authors: S
authors: S
authors: Laurent
authors: A
authors: A
authors: Deleporte
authors: P
authors: P
authors: Vergauwe
authors: A
authors: A
authors: Van Maanen
authors: C
authors: C
authors: Sempoux
authors: E
authors: E
authors: Van Cutsem
authors: J L
authors: JL
authors: Van Laethem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068818:Cetuximab; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D003841:Deoxycytidine; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D000093542:Gemcitabine
keywords: KRAS; cetuximab; chemotherapy; cholangiocarcinoma; gemcitabine