Cholangiocarcinoma medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Medical Therapy
Chemotherapy
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 has been shown in a randomized controlled trial to improve quality of life and extend survival in patients with inoperable cholangiocarcinoma.[2] There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible.[3] Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin,[4] gemcitabine as a single agent,[5] or gemcitabine plus cisplatin,[6] irinotecan,[7] or capecitabine.[8] A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in patients with advanced cholangiocarcinoma.[9] 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.
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].
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.
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.
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 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 excised), adjuvant therapy is of uncertain benefit. Both positive[10][11] and negative[12][13] results have been reported with adjuvant radiation therapy in this setting, and no prospective randomized controlled trials have been conducted as of March 2007. Adjuvant chemotherapy appears to be ineffective in patients with completely resected tumors.[14] 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.[3]
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 endoscopically directly to the tumor, has shown promising results compared to supportive care in two small randomized controlled trials. However, its ultimate role in the management of cholangiocarcinoma is unclear at present.[15][16]
References
- ↑ Vauthey J, Blumgart L (1994). "Recent advances in the management of cholangiocarcinomas". Semin. Liver Dis. 14 (2): 109–14. PMID 8047893.
- ↑ Glimelius B, Hoffman K, Sjödén P, Jacobsson G, Sellström H, Enander L, Linné T, Svensson C (1996). "Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer". Ann Oncol. 7 (6): 593–600. PMID 8879373.
- ↑ 3.0 3.1 Template:PDFlink. Accessed March 13 2007.
- ↑ Choi C, Choi I, Seo J, Kim B, Kim J, Kim C, Um S, Kim J, Kim Y (2000). "Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas". Am J Clin Oncol. 23 (4): 425–8. PMID 10955877.
- ↑ Park J, Oh S, Kim S, Kwon H, Kim J, Jin-Kim H, Kim Y (2005). "Single-agent gemcitabine in the treatment of advanced biliary tract cancers: a phase II study". Jpn J Clin Oncol. 35 (2): 68–73. PMID 15709089.
- ↑ Giuliani F, Gebbia V, Maiello E, Borsellino N, Bajardi E, Colucci G. "Gemcitabine and cisplatin for inoperable and/or metastatic biliary tree carcinomas: a multicenter phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM)". Ann Oncol. 17 Suppl 7: vii73–vii77. PMID 16760299.
- ↑ Bhargava P, Jani C, Savarese D, O'Donnell J, Stuart K, Rocha Lima C (2003). "Gemcitabine and irinotecan in locally advanced or metastatic biliary cancer: preliminary report". Oncology (Williston Park). 17 (9 Suppl 8): 23–6. PMID 14569844.
- ↑ Knox J, Hedley D, Oza A, Feld R, Siu L, Chen E, Nematollahi M, Pond G, Zhang J, Moore M (2005). "Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial". J Clin Oncol. 23 (10): 2332–8. PMID 15800324.
- ↑ Philip P, Mahoney M, Allmer C, Thomas J, Pitot H, Kim G, Donehower R, Fitch T, Picus J, Erlichman C (2006). "Phase II study of erlotinib in patients with advanced biliary cancer". J Clin Oncol. 24 (19): 3069–74. PMID 16809731.
- ↑ Todoroki T, Ohara K, Kawamoto T, Koike N, Yoshida S, Kashiwagi H, Otsuka M, Fukao K (2000). "Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma". Int J Radiat Oncol Biol Phys. 46 (3): 581–7. PMID 10701737.
- ↑ Alden M, Mohiuddin M (1994). "The impact of radiation dose in combined external beam and intraluminal Ir-192 brachytherapy for bile duct cancer". Int J Radiat Oncol Biol Phys. 28 (4): 945–51. PMID 8138448.
- ↑ González González D, Gouma D, Rauws E, van Gulik T, Bosma A, Koedooder C. "Role of radiotherapy, in particular intraluminal brachytherapy, in the treatment of proximal bile duct carcinoma". Ann Oncol. 10 Suppl 4: 215–20. PMID 10436826.
- ↑ Pitt H, Nakeeb A, Abrams R, Coleman J, Piantadosi S, Yeo C, Lillemore K, Cameron J (1995). "Perihilar cholangiocarcinoma. Postoperative radiotherapy does not improve survival". Ann Surg. 221 (6): 788–97, discussion 797-8. PMID 7794082.
- ↑ Takada T, Amano H, Yasuda H, Nimura Y, Matsushiro T, Kato H, Nagakawa T, Nakayama T (2002). "Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma". Cancer. 95 (8): 1685–95. PMID 12365016.
- ↑ 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.
- ↑ 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.