Radiochemotherapy followed by gemcitabine and capecitabine in extrahepatic bile duct cancer: a phase I/II trial.
OBJECTIVE
Both radiotherapy and chemotherapy with gemcitabine and capecitabine have efficacy in biliary cancer. Our aim was to determine the toxicity and efficacy of a postoperative regimen combining both treatment modalities in extrahepatic bile duct cancer.


METHODS
Patients were eligible after surgery for extrahepatic bile duct adenocarcinoma. Surgery included resection of lymph node positive cancer, incomplete resections and diagnostic laparotomy in unresectable tumors. Patients received a fractionated radiotherapy of 49.6 Gy accompanied by gemcitabine once a week. After a 2-week rest, patients were treated with gemcitabine and capecitabine on a 3-week cycle. The treatment continued for 6 cycles in nonmeasurable disease or until disease progression or intolerable toxicity.


RESULTS
There were 18 patients (resection/laparotomy 7/11) enrolled between August 2003 and April 2005. Radiotherapy was completed in all patients and a total of 66 cycles of chemotherapy was applied. Fatigue and nausea were the most common mild adverse events. Grade 3 and 4 toxicity was rare after resection but frequent in unresectable disease and consisted of fatigue, nausea, duodenal ulcer, cachexia, and cholangitis in 1, 2, 2, 4, and 4 patients, respectively. We observed a 50% disease stabilization rate in patients with measurable disease. Median overall survival was 7.9 months in patients with unresectable tumors. Median overall survival in patients after resection has not been reached at a median follow-up of 19.5 months.


CONCLUSIONS
Radiochemotherapy using gemcitabine followed by gemcitabine and capecitabine is an active regimen with manageable toxicity after resection of extrahepatic bile duct cancer but has significant toxicity in unresectable disease.
Schoppmeyer
Konrad
K
Department of Internal Medicine II, University of Leipzig, Leipzig, Germany. Konrad.Schoppmeyer@medizin.uni-leipzig.de
Miethe
Susanne
S
Wiedmann
Marcus
M
Liebmann
Andre
A
Hauss
Johann
J
Mossner
Joachim
J
Caca
Karel
K
Witzigmann
Helmut
H
Hildebrandt
Guido
G
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D017734:Bile Ducts, Extrahepatic; D000069287:Capecitabine; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil; D000093542:Gemcitabine