Effective treatment of advanced cholangiocarcinoma by hepatic arterial infusion chemotherapy combination with sorafenib: one case report from China.
OBJECTIVE
Cholangiocarcinoma, especially intrahepatic type, is difficult to be found early and diagnosed at early stages. Although it was reported as rare to happen, it is a well-known devastating malignancy with little treatment effects. As a result, most of the patients suffer from poor prognosis. On the other hand, the incidence of intrahepatic cholangiocarcinoma arises worldwide. Radical surgical resection was regarded as the most effective treatment, in spite of recurrence. Unfortunately, only 30 percent of patients qualify for this at the time of diagnosis. Hence, for advanced cholangiocarcinoma, chemotherapy is the only modality left to be chosen. Recently LaRocca and Kudoh reported about effective chemotherapy for cholangiocarcinoma. Even so, because of no randomized study, no standard chemotherapy for cholangiocarcinoma has been accepted, and most of the projects were based on 5-Fu. Sorafenib, a multikinase inhibitor, which can competitively inhibit RAF/MEK/ERK pathway, human vascular endothelial growth factor receptors (VEGFR2, VEGFR3) platelet-derived growth factor receptor beta (PDGFR), Flt3, and C-kit receptors, has been successfully applied for solid tumors such as renal cancer and hepatocellular carcinoma. Sorafenib used alone or in combinations, can induce growth-inhibition and apoptosis in vitro experiments. Application of sorafenib alone for cholangiocarcinoma has also been published. The role of combination with other chemotherapy drugs in advanced cholangiocarcinoma still needs to be defined.


METHODS
A patient admitted for exploratory operation was demonstrated to be suffering from unresectable, biopsy-proven intrahepatic cholangiocarcinoma. A pump was placed inside hepatic artery, for the purpose of infusion chemotherapy. Program of chemotherapy was scheduled and hepatic arterial infusion of 5-Fu/LV +oxaliplatin +hydroxycamptothecine was performed. Three months later, no effect was discovered, so sorafenib was suggested to combine with infusion chemotherapy. For the first time we applied sorafenib combination to hepatic arterial infusion chemotherapy


RESULTS
After lower dosage of sorafenib was used as a combination with hepatic arterial infusion chemotherapy, size of hepatic lesions and level CA19-9 of peripheral blood count were decreased, without any damage to the hepatic function, except for temporary skin hyperkeratosis as well as vomit. Efficacy of treatment was demonstrated by computed tomography (CT) scan.


CONCLUSIONS
So far as in our patient, the application of sorafenib combination with other agents through hepatic arterial infusion chemotherapy may be an effective way for cholangiocarcinoma, but the definite mechanism has to be confirmed by methods of molecular biology.
Qun
Wang
W
Department of Hepatopancreatobiliary Surgery, Hu bei Cancer Hospital No.116, South Zuo dao quan Road, Wuhan 430079, Hubei Province, China.
Tao
Yin
Y
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001557:Benzenesulfonates / Q000008:administration & dosage*; D001650:Bile Duct Neoplasms / Q000188:drug therapy*; D001653:Bile Ducts, Intrahepatic; D018395:CA-19-9 Antigen / Q000097:blood; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011725:Pyridines / Q000008:administration & dosage*; D000077157:Sorafenib
D001557:Benzenesulfonates; D018395:CA-19-9 Antigen; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib