title: A Phase II study of intravenous exatecan administered daily for 5 days, every 3 weeks to patients with biliary tract cancers.
abstract: OBJECTIVE
  Exatecan is a hexacyclic topoisomerase-1 inhibitor that has broad in vitro and in vivo activity. A multicenter phase II study to determine the antitumor activity of exatecan was conducted in patients with advanced cholangiocarcinoma and gallbladder carcinoma.
  
  
  METHODS
  Patients with 0 to 1 prior chemotherapy regimens, adequate major organ function, and metastatic disease were eligible. Exatecan was administered at a dose of 0.5 mg/m2 IV over 30 minutes daily on days 1 through 5 every 21 days. The primary end point was overall response rate: complete response and partial response (PR). A Simon optimal 2-stage design was employed. Response was assessed every 6 weeks.
  
  
  RESULTS
  Forty-two patients were enrolled. Two of 41 evaluated patients (4.9%) had a PR, 4 patients (9.8%) had a minor response, and 12 had stable disease. Twenty patients (51.2%) had progressive disease. The major toxicity was grade 3/4 neutropenia. The median overall survival was 7 months. The 6-month survival rate was 56.1% and the 12-month survival rate was 31.7%.
  
  
  CONCLUSIONS
  Exatecan has minimal activity in advanced biliary tree cancers. Toxicity was predictable and manageable.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York 10022, USA. abou-alg@mskcc.org
authors.forename: Ghassan K
authors.initials: GK
authors.lastname: Abou-Alfa
authors.forename: Eric K
authors.initials: EK
authors.lastname: Rowinsky
authors.forename: Yehuda Z
authors.initials: YZ
authors.lastname: Patt
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schwartz
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsen
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
authors.forename: Eve
authors.initials: E
authors.lastname: Siegel
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Becerra
authors.forename: S Gail
authors.initials: SG
authors.lastname: Eckhardt
authors.forename: Kevie
authors.initials: K
authors.lastname: Feit
authors.forename: Robert
authors.initials: R
authors.lastname: De Jager
authors.forename: Eileen M
authors.initials: EM
authors.lastname: O'Reilly
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000401:mortality; D001653:Bile Ducts, Intrahepatic; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000401:mortality; D004334:Drug Administration Schedule; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D059004:Topoisomerase I Inhibitors; D016896:Treatment Outcome
chemical_list: D059004:Topoisomerase I Inhibitors; C095887:exatecan; D002166:Camptothecin