Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver.
OBJECTIVE
In nonresectable cholangiocellular carcinoma (CCC) therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%. Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver.


METHODS
Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m(2)) and additional transarterial chemoembolization procedures (50 mg/m(2) cisplatin, 50 mg/m(2) doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity.


RESULTS
Both systemic and regional therapies were tolerated well; no severe toxicity (WHO III/IV) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered. Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases, stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo.


CONCLUSIONS
The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.
Kirchhoff
Timm
T
Department of Diagnostic Radiology, OE 8220, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany. kirchhoff.timm@mh-hannover.de
Zender
Lars
L
Merkesdal
Sonja
S
Frericks
Bernd
B
Malek
Nisar
N
Bleck
Joerg
J
Kubicka
Stefan
S
Baus
Stefan
S
Chavan
Ajay
A
Manns
Michael-P
MP
Galanski
Michael
M
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D001650:Bile Duct Neoplasms / Q000188:drug therapy*; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D004621:Embolization, Therapeutic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine