A Phase II study of intravenous exatecan administered daily for 5 days, every 3 weeks to patients with biliary tract cancers.
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.
Abou-Alfa
Ghassan K
GK
Memorial Sloan-Kettering Cancer Center, New York, New York 10022, USA. abou-alg@mskcc.org
Rowinsky
Eric K
EK
Patt
Yehuda Z
YZ
Schwartz
Gary K
GK
Kelsen
David P
DP
Sharma
Sunil
S
Siegel
Eve
E
Becerra
Carlos R
CR
Eckhardt
S Gail
SG
Feit
Kevie
K
De Jager
Robert
R
O'Reilly
Eileen M
EM
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
D059004:Topoisomerase I Inhibitors; C095887:exatecan; D002166:Camptothecin