- Case Report
- Open Access
A case of advanced intrahepatic cholangiocarcinoma accidentally, but successfully, treated with capecitabine plus oxaliplatin (CAPOX) therapy combined with bevacizumab: a case report
© The Author(s). 2016
- Received: 23 April 2016
- Accepted: 17 June 2016
- Published: 25 June 2016
Although surgical resection is the only way to cure biliary tract cancer (BTC), most BTCs are unresectable by the time they are diagnosed. Chemotherapy is usually used to treat unresectable BTC, but its impact on survival is small. Here, we report the case of a 70-year-old woman with a locally advanced intrahepatic cholangiocarcinoma that was initially diagnosed as an unresectable liver metastasis from colon cancer that had invaded all of the major hepatic veins. However, the tumor was noticeably reduced after treatment with CAPOX plus bevacizumab, which is an uncommon therapy for BTC. The tumor was finally resected by inferior right hepatic vein-preserving left hepatic trisectionectomy combined with a resection of the right hepatic vein after a right hepatic vein embolization.
- Inferior Vena Cava
- Hepatic Vein
Biliary tract cancer (BTC), which includes multiple cancers, such as cholangiocarcinoma and gallbladder carcinoma, is difficult to treat. Although surgical resection is the only way to cure, most patients with BTC are diagnosed at such a late stage that resection is not possible. Systemic chemotherapy is used for these patients [1, 2], and recently, combination therapy with gemcitabine and cisplatin (GC) has been recommended as the first-line regimen in these cases [3, 4]. A large phase III trial conducted in the UK added cisplatin to a gemcitabine therapy regimen and demonstrated a subsequent increase in response rate (26 vs 16 %) and increase in overall survival time (11.7 vs 8.1 months) . Other regimens of chemotherapy were assessed in several clinical trials, but the findings are inconsistent because of the limited number of patients who enrolled in the trials.
We herein report a case of intrahepatic cholangiocarcinoma that was accidentally, but successfully, treated with a new chemotherapy regimen that was not previously used to treat BTC.
Liver dysfunction was discovered in a 70-year-old woman at a local hospital. Abdominal ultrasonography revealed a hepatic mass, and she was referred to our hospital for possible surgery. On admission, laboratory tests showed mild elevations of AST, ALT, and γGTP. Serum levels of CEA and CA19-9 were 5.8 ng/L (normal range 0–5 ng/L) and 243 IU/mL (normal range 0–37 IU/mL), respectively.
Several clinical studies have assessed the clinical efficacy of various chemotherapy treatment regimens in patients with advanced BTC, but none of the studies evaluated CAPOX therapy combined with bevacizumab. Only one phase II trial assessed CAPOX therapy for BTC, which includes gallbladder carcinoma and extra- and intrahepatic cholangiocarcinomas, and the trial showed that the overall response rate (CR, PR, or SD) was 65 % . However, in patients with an intrahepatic cholangiocarcinoma, neither CR nor PR was achieved, and SD was observed in only 33 % of the patients, with a median overall survival time of 5.2 months. Thus, this phase II trial suggested that CAPOX therapy has no effect on intrahepatic cholangiocarcinoma.
Bevacizumab is an important therapeutic agent with promising results against some malignancies, and it is frequently given in conjunction with CAPOX therapy. The ability of this molecularly targeted drug, in combination with gemcitabine plus oxaliplatin (Gemox) or with erlotinib, to treat BTC was tested in two phase II trials [6–9]. The combination of Gemox plus bevacizumab showed promising results with a response rate of 40 % and a median overall survival time of 12.7 months . In patients with intrahepatic cholangiocarcinoma, the median overall survival time was 14.2 months. In contrast, bevacizumab plus erlotinib showed modest efficacy with a response rate of 12 % and a median overall survival of 9.9 months . Although the effect of CAPOX plus bevacizumab therapy for intrahepatic cholangiocarcinoma on survival is unclear, this combination regimen was very effective in the current case report. Vascular endothelial growth factor (VEGF) is expressed in approximately 50 % of intrahepatic cholangiocarcinomas , and anti-VEGF treatments result in pruning of the tumor vasculature and reductions in vessel tortuosity . MDCT images showed that the current patient had a hypervascular liver tumor. Microscopically, scattered unpaired arteries were found via immunostaining for heavy-caldesmon, a marker of vascular smooth muscle. These histological findings indicate that bevacizumab might be an effective treatment for intrahepatic cholangiocarcinoma.
In 1987, Makuuchi et al. reported the possibility of using IRHV-preserving left hepatic trisectionectomy with combined resection of the RHV . Thereafter, this challenging extended hepatectomy was performed in a few cases where the IRHV was “thick” [13, 14]. In cases where the IRHV is “thin,” however, this surgery can be risky; therefore, to overcome the risks, the use of RHV embolization was suggested by Nagino et al. . They proposed that preoperative RHV embolization be used when the RHV was large and the IRHV was medium or small . The IRHV in the patient in the current case was thin, approximately 0.5 cm in diameter and, therefore, was a good candidate for RHV embolization.
This was a rare case of advanced intrahepatic cholangiocarcinoma that was accidentally, but successfully, treated with a CAPOX plus bevacizumab regimen. The current case could provide insight for new chemotherapy regimen options to treat BTC.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in Chief of this journal.
BTC, biliary tract cancer; CAPOX, capecitabine plus oxialiplatin; CR, complete response; GC, gemcitabine plus oxaliplatin; GEMOX, gemcitabine plus oxaliplatin; IRHV, inferior right hepatic vein; IVC, inferior vena cava; LHV, left hepatic vein; MDCT, multidetector-row computed tomography; MHV, middle hepatic vein; PR, partial response; RHV, right hepatic vein; SD, stable disease; VEGF, vascular endothelial growth factor.
The authors declare that they have no competing interests.
MU, TE, GS, TI, KU, and TM performed surgery and perioperative management on the patient, and MN drafted the manuscript. All authors read and approved the final manuscript.
MU, TE, GS, TI, KU, TM, and MN are all staff surgeons of the Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine.
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- Miyazaki M, Yoshitomi H, Miyakawa S, Uesaka K, Unno M, Endo I. Clinical practice guidelines for the management of biliary tract cancers 2015: the 2 nd English edition. J Hepatobiliary Pancreat Sci. 2015;22(4):249–73.View ArticlePubMedGoogle Scholar
- Ramírez-merino N, Aix SP, Cortés-funes H. Chemotherapy for cholangiocarcinoma: an update. World J Gastrointest Oncol. 2013;5:171–6.View ArticlePubMedPubMed CentralGoogle Scholar
- Valle J, Wasan H, Palmer D, Cunningham D, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–81.Google Scholar
- Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010;103:469–74.View ArticlePubMedPubMed CentralGoogle Scholar
- Nehls O, Oettle H, Hartmann J, Hofheinz R-D, et al. Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial. Br J Cancer. 2008;98(2):309–15.Google Scholar
- Furuse J, Okusaka T. Targeted therapy for biliary tract cancer. Cancers (Basel). 2011;3:2243–54.View ArticleGoogle Scholar
- Faris JE, Zhu AX. Targeted therapy for biliary tract cancers. J Hepatobiliary Pancreat Sci. 2012;19:326–36.View ArticlePubMedGoogle Scholar
- Zhu AX, Meyerhardt JA, Blaszkowsky LS, Kambadakone AR, Muzikansky A, Zheng H, et al. Effi cacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fl uorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol. 2010;11:48–54.View ArticlePubMedGoogle Scholar
- Lubner SJ, Mahoney MR, Kolesar JL, LoConte NK, Kim GP, Pitot HC, et al. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II consortium study. J Clin Oncol. 2010;28:3491–7.View ArticlePubMedPubMed CentralGoogle Scholar
- Yoshikawa D, Ojima H, Iwasaki M, Hiraoka N, Kosuge T, Kasai S, et al. Clinicopathological and prognostic significance of EGFR, VEGF, and HER2 expression in cholangiocarcinoma. Br J Cancer. 2008;98:418–25.View ArticlePubMedGoogle Scholar
- Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies. Cancer Res. 2005;65:671–80.PubMedGoogle Scholar
- Makuuchi M, Hasegawa H, Yamazaki S, Takayasu K. Four new hepatectomy procedures for resection of the right hepatic vein and preservation of the inferior right hepatic vein. Surg Gynecol Obstet. 1987;164:68–72.PubMedGoogle Scholar
- Baer HU, Dennison AR, Maddern GJ, Blumgart LH. Subtotal hepatectomy: a new procedure based on the inferior right hepatic vein. Br J Surg. 1991;78(10):1221–2.View ArticlePubMedGoogle Scholar
- Ozeki Y, Uchiyama T, Katayama M, Sugiyama A, Kokubo M, Matsubara N. Extended left hepatic trisegmentectomy with resection of main right hepatic vein and preservation of middle and inferior hepatic veins. Surgery. 1995;117:715–7.View ArticlePubMedGoogle Scholar
- Nagino M, Yamada T, Kamiya J, Uesaka K, Arai T, Nimura Y. Left hepatic trisegmentectomy with right hepatic vein resection after right hepatic vein embolization. Surgery. 2003;133:580–2.View ArticlePubMedGoogle Scholar
- Nakamura S, Tsuzuki T. Surgical anatomy of the hepatic veins and the inferior vena cava. Surg Gynecol Obstet. 1981;152:43–50.PubMedGoogle Scholar