title: A phase II trial of gemcitabine, irinotecan and panitumumab in advanced cholangiocarcinoma.
abstract: BACKGROUND
  Current data suggest that chemotherapy combinations may be superior to single agents in biliary tract cancer. The epidermal growth factor receptor (EGFR) pathway appears to be associated with tumor stage, prognosis and response to therapy. This trial was designed to evaluate the tolerability and efficacy of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan.
  
  
  METHODS
  Patients with advanced (unresectable or metastatic) cholangiocarcinoma, ECOG PS 0-2, and adequate organ function were treated with panitumumab (9 mg/kg) on day 1, and gemcitabine (1000 mg/m(2)) and irinotecan (100 mg/m(2)) on days 1 and 8 of a 21-day cycle. The primary objective was to evaluate the 5-month progression-free survival (PFS). Secondary objectives included overall response rate (ORR) and overall survival (OS). Mutational analyses of EGFR, KRAS and BRAF were carried out when feasible.
  
  
  RESULTS
  Thirty-five patients received a median of 7 (0-30) cycles. The most common grade 3/4 toxic effects were neutropenia (10 patients, 29%), thrombocytopenia (10 patients, 29%), skin rash (13 patients, 37%) and dehydration (9 patients, 26%). Two patients had CR, 9 had partial response (PR), and 15 had SD for a disease-control rate of 74% (by RECIST) in 28 assessable patients. Two patients went on to have surgical resection. The 5-month PFS was 69%. The median PFS was 9.7 months and the median OS was 12.9 months. In 17 testable samples, no EGFR or BRAF mutations were identified; there were 7 KRAS mutations, with no difference in OS by KRAS status.
  
  
  CONCLUSIONS
  This study showed encouraging efficacy of this regimen with good tolerability. Further study in this area is warranted. Clinical Trials Number: The trial was registered with the National Cancer Institute (www.clinicaltrials.gov identifier NCT00948935).
authors.affiliation: Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA.
authors.forename: D P S
authors.initials: DP
authors.lastname: Sohal
authors.forename: K
authors.initials: K
authors.lastname: Mykulowycz
authors.forename: T
authors.initials: T
authors.lastname: Uehara
authors.forename: U R
authors.initials: UR
authors.lastname: Teitelbaum
authors.forename: N
authors.initials: N
authors.lastname: Damjanov
authors.forename: B J
authors.initials: BJ
authors.lastname: Giantonio
authors.forename: M
authors.initials: M
authors.lastname: Carberry
authors.forename: P
authors.initials: P
authors.lastname: Wissel
authors.forename: M
authors.initials: M
authors.lastname: Jacobs-Small
authors.forename: P J
authors.initials: PJ
authors.lastname: O'Dwyer
authors.forename: A
authors.initials: A
authors.lastname: Sepulveda
authors.forename: W
authors.initials: W
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004252:DNA Mutational Analysis; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000077544:Panitumumab; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D003841:Deoxycytidine; D000077544:Panitumumab; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002166:Camptothecin; D000093542:Gemcitabine
keywords: biliary tract cancer; cholangiocarcinoma; epidermal growth factor receptor EGFR; gemcitabine; irinotecan; panitumumab