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__NOTOC__
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{{Cholangiocarcinoma}}
{{Cholangiocarcinoma}}
{{CMG}}
{{CMG}};{{AE}} {{F.K}}, {{PSK}}
 
==Overview==
==Overview==
Chemotherapy is indicated for unresectable cholangiocarcinoma as [[palliation|palliative chemotherapy]]. Chemotherapy agents used to treat cholangiocarcinoma include [[5-fluorouracil]], [[gemcitabine]], [[irinotecan]], [[cisplatin]], or [[doxorubicin]].
==Medical Therapy==
==Medical Therapy==
The majority of cases of cholangiocarcinoma present as unresectable disease.<ref>{{cite journal |author=Vauthey J, Blumgart L |title=Recent advances in the management of cholangiocarcinomas |journal=Semin. Liver Dis. |volume=14 |issue=2 |pages=109-14 |year=1994 |pmid=8047893}}</ref> If the tumor cannot be surgically removed, patients are often treated with [[palliation|palliative]] [[chemotherapy]] with or without [[radiotherapy]].
===Chemotherapy===
===Chemotherapy===
The majority of cases of cholangiocarcinoma present as unresectable disease.<ref>{{cite journal |author=Vauthey J, Blumgart L |title=Recent advances in the management of cholangiocarcinomas |journal=Semin. Liver Dis. |volume=14 |issue=2 |pages=109-14 |year=1994 |pmid=8047893}}</ref> If the tumor cannot be surgically removed, patients are often treated with [[palliation|palliative]] [[chemotherapy]] with or without [[radiotherapy]].  Chemotherapy has been shown in a [[randomized controlled trial]] to improve [[quality of life]] and extend survival in patients with inoperable cholangiocarcinoma.<ref>{{cite journal |author=Glimelius B, Hoffman K, Sjödén P, Jacobsson G, Sellström H, Enander L, Linné T, Svensson C |title=Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer |journal=Ann Oncol |volume=7 |issue=6 |pages=593–600 |year=1996 |id=PMID 8879373}}</ref> There is no single chemotherapy regimen which is universally used, and enrollment in [[clinical trial]]s is often recommended when possible.<ref name="nccn"/> Chemotherapy agents used to treat cholangiocarcinoma include [[5-fluorouracil]] with [[leucovorin]],<ref>{{cite journal |author=Choi C, Choi I, Seo J, Kim B, Kim J, Kim C, Um S, Kim J, Kim Y |title=Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas |journal=Am J Clin Oncol |volume=23 |issue=4 |pages=425-8 |year=2000 |pmid=10955877}}</ref> [[gemcitabine]] as a single agent,<ref>{{cite journal |author=Park J, Oh S, Kim S, Kwon H, Kim J, Jin-Kim H, Kim Y |title=Single-agent gemcitabine in the treatment of advanced biliary tract cancers: a phase II study |journal=Jpn J Clin Oncol |volume=35 |issue=2 |pages=68–73 |year=2005 |pmid=15709089}}</ref> or gemcitabine plus [[cisplatin]],<ref>{{cite journal |author=Giuliani F, Gebbia V, Maiello E, Borsellino N, Bajardi E, Colucci G |title=Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM) |journal=Ann Oncol |volume=17 Suppl 7 |issue= |pages=vii73-vii77 |year= |pmid=16760299}}</ref> [[irinotecan]],<ref>{{cite journal |author=Bhargava P, Jani C, Savarese D, O'Donnell J, Stuart K, Rocha Lima C |title=Gemcitabine and irinotecan in locally advanced or metastatic biliary cancer: preliminary report |journal=Oncology (Williston Park) |volume=17 |issue=9 Suppl 8 |pages=23-6 |year=2003 |pmid=14569844}}</ref> or [[capecitabine]].<ref>{{cite journal |author=Knox J, Hedley D, Oza A, Feld R, Siu L, Chen E, Nematollahi M, Pond G, Zhang J, Moore M |title=Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial |journal=J Clin Oncol |volume=23 |issue=10 |pages=2332–8 |year=2005 |pmid=15800324}}</ref> A small pilot study suggested possible benefit from the [[tyrosine kinase]] inhibitor [[erlotinib]] in patients with advanced cholangiocarcinoma.<ref>{{cite journal |author=Philip P, Mahoney M, Allmer C, Thomas J, Pitot H, Kim G, Donehower R, Fitch T, Picus J, Erlichman C |title=Phase II study of erlotinib in patients with advanced biliary cancer |journal=J Clin Oncol |volume=24 |issue=19 |pages=3069–74 |year=2006 |pmid=16809731}}</ref>
* 1.'''Chemotherapy'''
The currently available adjuvant therapies, chemotherapy, and radiotherapy have not been shown to improve the outcome or time to recurrence of patients when administered either before or after surgery, although no large randomized trials have been conducted. It has even been reported that radiation therapy may elicit unwanted results, such as difficulties in handling cholangiopathies.
** Preferred regimen (1): [[5-fluorouracil]] 600 mg/m2 with [[leucovorin]] 400 mg/m2 over 2 hours once every 2 weeks <ref name="pmid23919111">{{cite journal |vauthors=Ramírez-Merino N, Aix SP, Cortés-Funes H |title=Chemotherapy for cholangiocarcinoma: An update |journal=World J Gastrointest Oncol |volume=5 |issue=7 |pages=171–6 |year=2013 |pmid=23919111 |pmc=3731530 |doi=10.4251/wjgo.v5.i7.171 |url=}}</ref>  
** Alternative regimen (2): [[Gemcitabine]] 1,000 mg/m2 plus cisplatin <ref name="pmid15800324">{{cite journal |vauthors=Knox JJ, Hedley D, Oza A, Feld R, Siu LL, Chen E, Nematollahi M, Pond GR, Zhang J, Moore MJ |title=Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial |journal=J. Clin. Oncol. |volume=23 |issue=10 |pages=2332–8 |year=2005 |pmid=15800324 |doi=10.1200/JCO.2005.51.008 |url=}}</ref>
** Alternative regimen (3): [[Irinotecan]] 125 mg/m2 q14 days
** Alternative regimen (4): [[Oxaliplatin]] 400 mg/m2 <ref name="pmid15319238">{{cite journal |vauthors=André T, Tournigand C, Rosmorduc O, Provent S, Maindrault-Goebel F, Avenin D, Selle F, Paye F, Hannoun L, Houry S, Gayet B, Lotz JP, de Gramont A, Louvet C |title=Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study |journal=Ann. Oncol. |volume=15 |issue=9 |pages=1339–43 |year=2004 |pmid=15319238 |doi=10.1093/annonc/mdh351 |url=}}</ref>
** Alternative regimen (5): [[Doxorubicin]] 60-75 mg/m2 q21 days <ref name="pmid11705850">{{cite journal |vauthors=Patt YZ, Hassan MM, Lozano RD, Waugh KA, Hoque AM, Frome AI, Lahoti S, Ellis L, Vauthey JN, Curley SA, Schnirer II, Raijman I |title=Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer |journal=Clin. Cancer Res. |volume=7 |issue=11 |pages=3375–80 |year=2001 |pmid=11705850 |doi= |url=}}</ref>
** Alternative regimen (6): [[Capecitabine]] 650 mg/m2 q21 days for 2 weeks
** Alternative regimen (7): [[Erlotinib]] PO 100 mg/day


For some patients with non-operable tumors, biliary drainage through a tiny metal or plastic tube (‘‘biliary stent’’) may result in an improvement of the patient’s situation due to relief of the obstructive cholestasis. This can be done percutaneously, although with these external drainage systems patients may experience certain discomfort, and it is the only option in cases of complete biliary obstruction. Stents may eventually cease to function because of tumor overgrowth, obstruction, or other reasons; plastic stents need to be changed every 3 months, while metal stents can be maintained for longer times [72]. Cholestasis is a risk factor for hepatic failure after liver resection and stents are now widely used for preoperative drainage. Self-expanding metal stents are preferred because they provide rapid biliary decompression and a reduced complication rate after insertion [73].
===Regional therapies===
*Regional therapies is recommended among patients with small cholangiocarcinomas, when the general health condition of the patient does not allow a more aggressive treatment:<ref name="pmid22627601">{{cite journal |vauthors=Halappa VG, Bonekamp S, Corona-Villalobos CP, Li Z, Mensa M, Reyes D, Eng J, Bhagat N, Pawlik TM, Geschwind JF, Kamel IR |title=Intrahepatic cholangiocarcinoma treated with local-regional therapy: quantitative volumetric apparent diffusion coefficient maps for assessment of tumor response |journal=Radiology |volume=264 |issue=1 |pages=285–94 |year=2012 |pmid=22627601 |doi=10.1148/radiol.12112142 |url=}}</ref><ref name="pmid21460876">{{cite journal |vauthors=Patel T |title=Cholangiocarcinoma--controversies and challenges |journal=Nat Rev Gastroenterol Hepatol |volume=8 |issue=4 |pages=189–200 |year=2011 |pmid=21460876 |pmc=3888819 |doi=10.1038/nrgastro.2011.20 |url=}}</ref>
**[[Transcatheter arterial chemoembolization|Transarterial chemoembolization]] ([[Transcatheter arterial chemoembolization|TACE]])
**[[Therapeutic embolization|Radioembolization]]


Evaluation of the clinical usefulness of other therapeutical strategies that have emerged in recent years requires further investigation. Thus, photodynamic therapy seems to relieve pain, improves the flow of bile through the biliary tree, and increases survival.
===Photodynamic Therapy===
 
*[[Photodynamic therapy]]
'''Transarterial chemoembolization (TACE)''', which increases the local concentration of chemotherapeutic agents and reduces systemic exposure, has shown promising results, increasing survival, and '''radioembolization''' also seems to increase survival. Thus, these regional therapies are considered as an option for treating small tumors when the general health condition of the patient does not permit a more aggressive treatment.
**Injected with a light-sensitizing agent and light is then applied [[endoscopy|endoscopically]] directly to the tumor <ref>{{cite journal |author=Ortner M, Caca K, Berr F, Liebetruth J, Mansmann U, Huster D, Voderholzer W, Schachschal G, Mössner J, Lochs H |title=Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study |journal=Gastroenterology |volume=125 |issue=5 |pages=1355–63 |year=2003 |pmid=14598251}}</ref><ref>{{cite journal |author=Zoepf T, Jakobs R, Arnold J, Apel D, Riemann J |title=Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy |journal=Am J Gastroenterol |volume=100 |issue=11 |pages=2426–30 |year=2005 |pmid=16279895}}</ref>
 
An important number of phase-II clinical trials have been carried out with different chemotherapy regimes to treat cholangiocarcinoma, using single or combined agents (Table 5). In contrast, to date the number of phase-III trials has been low. These studies have some limitations, mainly due to the heterogeneity of the tumor types included (grouped as biliary tract cancer in some studies, or cholangiocarcinoma without separation between types), different extents of the disease, naïve patients mixed together with patients who have previously received different therapies, small numbers of patients included, and so forth. This has contributed to the fact that, even though the moderate benefits and tolerability of some regimes have been described, as commented below, no standard treatment for cholangiocarcinoma has yet been established.
 
 
If the tumor can be removed surgically, patients may receive [[adjuvant#oncology|adjuvant]] [[chemotherapy]] or [[radiation therapy]] after the operation to improve the chances of cure. If the tissue margins are negative (i.e. the tumor has been totally [[excision|excised]]), adjuvant therapy is of uncertain benefit. Both positive<ref>{{cite journal |author=Todoroki T, Ohara K, Kawamoto T, Koike N, Yoshida S, Kashiwagi H, Otsuka M, Fukao K |title=Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma |journal=Int J Radiat Oncol Biol Phys |volume=46 |issue=3 |pages=581-7 |year=2000 |pmid=10701737}}</ref><ref>{{cite journal |author=Alden M, Mohiuddin M |title=The impact of radiation dose in combined external beam and intraluminal Ir-192 brachytherapy for bile duct cancer |journal=Int J Radiat Oncol Biol Phys |volume=28 |issue=4 |pages=945-51 |year=1994 |pmid=8138448}}</ref> and negative<ref>{{cite journal |author=González González D, Gouma D, Rauws E, van Gulik T, Bosma A, Koedooder C |title=Role of radiotherapy, in particular intraluminal brachytherapy, in the treatment of proximal bile duct carcinoma |journal=Ann Oncol |volume=10 Suppl 4 |issue= |pages=215-20 |year= |pmid=10436826}}</ref><ref>{{cite journal |author=Pitt H, Nakeeb A, Abrams R, Coleman J, Piantadosi S, Yeo C, Lillemore K, Cameron J |title=Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival |journal=Ann Surg |volume=221 |issue=6 |pages=788–97; discussion 797-8 |year=1995 |pmid=7794082}}</ref> results have been reported with adjuvant radiation therapy in this setting, and no prospective [[randomized controlled trial]]s have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in patients with completely resected tumors.<ref>{{cite journal |author=Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T |title=Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma |journal=Cancer |volume=95 |issue=8 |pages=1685–95 |year=2002 |pmid=12365016}}</ref> The role of combined chemoradiotherapy in this setting is unclear. However, if the tumor tissue margins are positive, indicating that the tumor was not completely removed via surgery, then adjuvant therapy with radiation and possibly chemotherapy is generally recommended based on the available data.<ref name="nccn">{{PDFlink|[http://www.nccn.org/professionals/physician_gls/PDF/hepatobiliary.pdf National Comprehensive Cancer Network (NCCN) guidelines on evaluation and treatment of hepatobiliary malignancies]|216&nbsp;[[Kibibyte|KiB]]<!-- application/pdf, 221777 bytes -->}}. Accessed [[March 13]] [[2007]].</ref>
 
==Treatment of Advanced Disease==
 
 
====Photodynamic Therapy====
[[Photodynamic therapy]], an experimental approach in which patients are injected with a light-sensitizing agent and light is then applied [[endoscopy|endoscopically]] directly to the tumor, has shown promising results compared to supportive care in two small [[randomized controlled trial]]s. However, its ultimate role in the management of cholangiocarcinoma is unclear at present.<ref>{{cite journal |author=Ortner M, Caca K, Berr F, Liebetruth J, Mansmann U, Huster D, Voderholzer W, Schachschal G, Mössner J, Lochs H |title=Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study |journal=Gastroenterology |volume=125 |issue=5 |pages=1355–63 |year=2003 |pmid=14598251}}</ref><ref>{{cite journal |author=Zoepf T, Jakobs R, Arnold J, Apel D, Riemann J |title=Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy |journal=Am J Gastroenterol |volume=100 |issue=11 |pages=2426–30 |year=2005 |pmid=16279895}}</ref>


==References==
==References==
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Latest revision as of 15:43, 7 January 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Farima Kahe M.D. [2], Suveenkrishna Pothuru, M.B,B.S. [3]

Overview

Chemotherapy is indicated for unresectable cholangiocarcinoma as palliative chemotherapy. Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil, gemcitabine, irinotecan, cisplatin, or doxorubicin.

Medical Therapy

The majority of cases of cholangiocarcinoma present as unresectable disease.[1] If the tumor cannot be surgically removed, patients are often treated with palliative chemotherapy with or without radiotherapy.

Chemotherapy

Regional therapies

Photodynamic Therapy

References

  1. ↑ Vauthey J, Blumgart L (1994). "Recent advances in the management of cholangiocarcinomas". Semin. Liver Dis. 14 (2): 109–14. PMID 8047893.
  2. ↑ Ramírez-Merino N, Aix SP, Cortés-Funes H (2013). "Chemotherapy for cholangiocarcinoma: An update". World J Gastrointest Oncol. 5 (7): 171–6. doi:10.4251/wjgo.v5.i7.171. PMC 3731530. PMID 23919111.
  3. ↑ Knox JJ, Hedley D, Oza A, Feld R, Siu LL, Chen E, Nematollahi M, Pond GR, Zhang J, Moore MJ (2005). "Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial". J. Clin. Oncol. 23 (10): 2332–8. doi:10.1200/JCO.2005.51.008. PMID 15800324.
  4. ↑ André T, Tournigand C, Rosmorduc O, Provent S, Maindrault-Goebel F, Avenin D, Selle F, Paye F, Hannoun L, Houry S, Gayet B, Lotz JP, de Gramont A, Louvet C (2004). "Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study". Ann. Oncol. 15 (9): 1339–43. doi:10.1093/annonc/mdh351. PMID 15319238.
  5. ↑ Patt YZ, Hassan MM, Lozano RD, Waugh KA, Hoque AM, Frome AI, Lahoti S, Ellis L, Vauthey JN, Curley SA, Schnirer II, Raijman I (2001). "Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer". Clin. Cancer Res. 7 (11): 3375–80. PMID 11705850.
  6. ↑ Halappa VG, Bonekamp S, Corona-Villalobos CP, Li Z, Mensa M, Reyes D, Eng J, Bhagat N, Pawlik TM, Geschwind JF, Kamel IR (2012). "Intrahepatic cholangiocarcinoma treated with local-regional therapy: quantitative volumetric apparent diffusion coefficient maps for assessment of tumor response". Radiology. 264 (1): 285–94. doi:10.1148/radiol.12112142. PMID 22627601.
  7. ↑ Patel T (2011). "Cholangiocarcinoma--controversies and challenges". Nat Rev Gastroenterol Hepatol. 8 (4): 189–200. doi:10.1038/nrgastro.2011.20. PMC 3888819. PMID 21460876.
  8. ↑ Ortner M, Caca K, Berr F, Liebetruth J, Mansmann U, Huster D, Voderholzer W, Schachschal G, Mössner J, Lochs H (2003). "Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study". Gastroenterology. 125 (5): 1355–63. PMID 14598251.
  9. ↑ Zoepf T, Jakobs R, Arnold J, Apel D, Riemann J (2005). "Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy". Am J Gastroenterol. 100 (11): 2426–30. PMID 16279895.

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