Cholangiocarcinoma medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Adjuvant Chemotherapy and Radiation Therapy

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[1][2] and negative[3][4] 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.[5] 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.[6]

Treatment of Advanced Disease

Chemotherapy

The majority of cases of cholangiocarcinoma present as unresectable disease.[7] 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.[8] There is no single chemotherapy regimen which is universally used, and enrollment in clinical trials is often recommended when possible.[6] Chemotherapy agents used to treat cholangiocarcinoma include 5-fluorouracil with leucovorin,[9] gemcitabine as a single agent,[10] or gemcitabine plus cisplatin,[11] irinotecan,[12] or capecitabine.[13] A small pilot study suggested possible benefit from the tyrosine kinase inhibitor erlotinib in patients with advanced cholangiocarcinoma.[14]

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

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 6.0 6.1 National Comprehensive Cancer Network (NCCN) guidelines on evaluation and treatment of hepatobiliary malignanciesPDF (216 KiB). Accessed March 13 2007.
  7. Vauthey J, Blumgart L (1994). "Recent advances in the management of cholangiocarcinomas". Semin. Liver Dis. 14 (2): 109-14. PMID 8047893.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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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