title: Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver.
abstract: 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.
authors.affiliation: Department of Diagnostic Radiology, OE 8220, Hannover Medical School, Carl-Neuberg Str.1, D-30625 Hannover, Germany. kirchhoff.timm@mh-hannover.de
authors.forename: Timm
authors.initials: T
authors.lastname: Kirchhoff
authors.forename: Lars
authors.initials: L
authors.lastname: Zender
authors.forename: Sonja
authors.initials: S
authors.lastname: Merkesdal
authors.forename: Bernd
authors.initials: B
authors.lastname: Frericks
authors.forename: Nisar
authors.initials: N
authors.lastname: Malek
authors.forename: Joerg
authors.initials: J
authors.lastname: Bleck
authors.forename: Stefan
authors.initials: S
authors.lastname: Kubicka
authors.forename: Stefan
authors.initials: S
authors.lastname: Baus
authors.forename: Ajay
authors.initials: A
authors.lastname: Chavan
authors.forename: Michael-P
authors.initials: MP
authors.lastname: Manns
authors.forename: Michael
authors.initials: M
authors.lastname: Galanski
mesh_terms: 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
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine