Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 1, pp 191–198 | Cite as

Efficacy of concurrent chemoradiotherapy with 5-fluorouracil or gemcitabine in locally advanced biliary tract cancer

  • Seung Woo Yi
  • Dae Ryong Kang
  • Kyung Sik Kim
  • Mi Suk Park
  • Jinsil Seong
  • Jeong Youp Park
  • Seung Min Bang
  • Si Young Song
  • Jae Bock Chung
  • Seung Woo Park
Original Article

Abstract

Purpose

There is no established standard treatment for patients with locally advanced biliary tract cancer (BTC).

Methods

We analyzed the treatment results of locally advanced BTC from Jan 1995 to Dec 2010 at single institution of South Korea with retrospective study. One hundred and seventy-six patients were eligible to investigate the treatment response and toxicity. We treated these patients with 5-fluorouracil (5-FU)- or gemcitabine (GEM)-based concurrent chemoradiotherapy (CCRT) or best supportive care (BSC). The primary end point was overall survival.

Results

Of these locally advanced BTC patients, 106 patients received CCRT and 70 patients were treated with BSC. The median overall survival was 42.57 weeks (95 % confidence interval [CI], 35.85–49.30) in CCRT group and 13.29 weeks (95 % CI 10.42–16.15) in BSC group (P < 0.001). Nausea and anemia were the most common toxicities observed.

Conclusions

Patients with locally advanced BTC who were treated with 5-FU-based or GEM-based CCRT seem to have a better survival than those who received BSC. The treatment-related toxicity was mild. GEM-based or 5-FU-based CCRT showed similar survival advantages.

Keywords

Biliary tract cancer Concurrent chemoradiation GB cancer Locally advanced 

References

  1. 1.
    Shaib YH, Davila JA, McGlynn K, El-Serag HB (2004) Rising incidence of intrahepatic cholangiocarcinoma in the United States: a true increase? J Hepatol 40:472–477PubMedCrossRefGoogle Scholar
  2. 2.
    Shaib Y, El-Serag HB (2004) The Epidemiology of Cholangiocarcinoma. Semin Liver Dis 24:115–125PubMedCrossRefGoogle Scholar
  3. 3.
    West J, Wood H, Logan RF, Quinn M, Aithal GP (2006) Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001. Br J Cancer 94:1751–1758PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Jung KW, Park S, Kong HJ, Won YJ, Lee JY, Park EC, Lee J-S (2011) Cancer Statistics in Korea: incidence, mortality, survival, and prevalence in 2008. Cancer Res Treat 43:1–11PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Benjamin IS (1999) Surgical possibilities for bile duct cancer: standard surgical treatment. Ann Oncol 10:S239–S242. doi:10.1093/annonc/10.suppl_4.S239 CrossRefGoogle Scholar
  6. 6.
    Ducreux M, Van Cutsem E, Van Laethem JL, Gress TM, Jeziorski K, Rougier P, Wagener T, Anak O, Baron B, Nordlinger B (2005) A randomised phase II trial of weekly high-dose 5-fluorouracil with and without folinic acid and cisplatin in patients with advanced biliary tract carcinoma: results of the 40955 EORTC trial. Eur J Cancer 41:398–403. doi:10.1016/j.ejca.2004.10.026 PubMedCrossRefGoogle Scholar
  7. 7.
    Glimelius B, Hoffman K, Sjoden PO, Jacobsson G, Sellstrom H, Enander LK, Linne T, Svensson C (1996) Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol 7:593–600PubMedCrossRefGoogle Scholar
  8. 8.
    Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362:1273–1281. doi:10.1056/NEJMoa0908721 PubMedCrossRefGoogle Scholar
  9. 9.
    Park JS, Oh SY, Kim SH, Kwon HC, Kim JS, Jin-Kim H, Kim YH (2005) Single-agent gemcitabine in the treatment of advanced biliary tract cancers: a phase II study. Jpn J Clin Oncol 35:68–73PubMedCrossRefGoogle Scholar
  10. 10.
    Androulakis N, Aravantinos G, Syrigos K, Polyzos A, Ziras N, Tselepatiotis E, Samonis G, Kentepozidis N, Giassas S, Vamvakas L, Georgoulias V (2006) Oxaliplatin as first-line treatment in inoperable biliary tract carcinoma. Oncology 70:280–284PubMedCrossRefGoogle Scholar
  11. 11.
    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 23:2332–2338PubMedCrossRefGoogle Scholar
  12. 12.
    Cereda S, Passoni P, Reni M, Viganò MG, Aldrighetti L, Nicoletti R, Villa E (2010) The cisplatin, epirubicin, 5-fluorouracil, gemcitabine (PEFG) regimen in advanced biliary tract adenocarcinoma. Cancer, pp 2208–2214. doi:10.1002/cncr.24970
  13. 13.
    Philip PA, Mahoney MR, Allmer C, Thomas J, Pitot HC, Kim G, Donehower RC, Fitch T, Picus J, Erlichman C (2006) Phase II Study of erlotinib in patients with advanced biliary cancer. J Clin Oncol 24:3069–3074. doi:10.1200/jco.2005.05.3579 PubMedCrossRefGoogle Scholar
  14. 14.
    Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BSJ, Youssef BAM, Klimstra D, Blumgart LH (2001) Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg 234:507–519PubMedCrossRefGoogle Scholar
  15. 15.
    Jarnagin WR, Shoup M (2004) Surgical management of cholangiocarcinoma. Semin Liver Dis 24:189–199PubMedCrossRefGoogle Scholar
  16. 16.
    Beltrán MB, Roth AD, Mentha G, Allal AS (2011) Adjuvant radio-chemotherapy for extrahepatic biliary tract cancers. BMC Cancer 11:267. doi:10.1186/1471-2407-11-267 CrossRefGoogle Scholar
  17. 17.
    Park JY, Park SW, Chung JB, Seong J, Kim KS, Lee WJ, Song SY (2006) Concurrent chemoradiotherapy with doxifluridine and paclitaxel for extrahepatic bile duct cancer. Am J Clin Oncol 29:240–245. doi:10.1097/01.coc.0000217829.77404.22 PubMedCrossRefGoogle Scholar
  18. 18.
    Deodato F, Clemente G, Mattiucci GC, Macchia G, Costamagna G, Giuliante F, Smaniotto D, Luzi S, Valentini V, Mutignani M, Nuzzo G, Cellini N, Morganti AG (2006) Chemoradiation and brachytherapy in biliary tract carcinoma: long-term results. Int J Radiat Oncol Biol Phys 64:483–488PubMedCrossRefGoogle Scholar
  19. 19.
    Crane CH, Macdonald KO, Vauthey JN, Yehuda P, Brown T, Curley S, Wong A, Delclos M, Charnsangavej C, Janjan NA (2002) Limitations of conventional doses of chemoradiation for unresectable biliary cancer. Int J Radiat Oncol Biol Phys 53:969–974PubMedCrossRefGoogle Scholar
  20. 20.
    Kresl JJ, Schild SE, Henning GT, Gunderson LL, Donohue J, Pitot H, Haddock MG, Nagorney D (2002) Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma. Int J Radiat Oncol Biol Phys 52:167–175PubMedCrossRefGoogle Scholar
  21. 21.
    Alberts SR, Al-Khatib H, Mahoney MR, Burgart L, Cera PJ, Flynn PJ, Finch TR, Levitt R, Windschitl HE, Knost JA, Tschetter LK (2005) Gemcitabine, 5-fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma: a North Central Cancer Treatment Group phase II trial. Cancer 103:111–118PubMedCrossRefGoogle Scholar
  22. 22.
    Golfieri R, Giampalma E, Renzulli M, Galuppi A, Vicenzi L, Galaverni MC, Cappelli A (2006) Unresectable hilar cholangiocarcinoma: multimodality approach with percutaneous treatment associated with radiotherapy and chemotherapy. In Vivo 20:757–760PubMedGoogle Scholar
  23. 23.
    McMasters KM, Tuttle TM, Leach SD, Rich T, Cleary KR, Evans DB, Curley SA (1997) Neoadjuvant chemoradiation for extrahepatic cholangiocarcinoma. Am J Surg 174:605–609PubMedCrossRefGoogle Scholar
  24. 24.
    Hezel AF, Zhu AX (2008) Systemic therapy for biliary tract cancers. Oncologist 13:415–423. doi:10.1634/theoncologist.2007-0252 PubMedCrossRefGoogle Scholar
  25. 25.
    Polistina FA, Guglielmi R, Baiocchi C, Francescon P, Scalchi P, Febbraro A, Costantin G, Ambrosino G (2011) Chemoradiation treatment with gemcitabine plus stereotactic body radiotherapy for unresectable, non-metastatic, locally advanced hilar cholangiocarcinoma. Results of a five year experience. Radiother Oncol 99:120–123. doi:10.1016/j.radonc.2011.05.016 PubMedCrossRefGoogle Scholar
  26. 26.
    Lin MH, Chen JS, Chen HHW, Su WC (2003) A phase ii trial of gemcitabine in the treatment of advanced bile duct and periampullary carcinomas. Chemotherapy 49:154–158PubMedCrossRefGoogle Scholar
  27. 27.
    Heron DE, Stein DE, Eschelman DJ, Topham AK, Waterman FM, Rosato EL, Alden MM, Anne PR (2003) Cholangiocarcinoma: the impact of tumor location and treatment strategy on outcome. Am J Clin Oncol 26:422–428PubMedGoogle Scholar
  28. 28.
    Ben-David MA, Griffith KA, Abu-Isa E, Lawrence TS, Knol J, Zalupski M, Ben-Josef E (2006) External-beam radiotherapy for localized extrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys 66:772–779PubMedCrossRefGoogle Scholar
  29. 29.
    Habermehl D, Lindel K, Rieken S, Haase K, Goeppert B, Büchler MW, Schirmacher P, Welzel T, Debus J, Combs SE (2012) Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection: analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation. Strahlenther Onkol 188(9):795–801PubMedCrossRefGoogle Scholar
  30. 30.
    Ishii H, Furuse J, Yonemoto N, Nagase M, Yoshino M, Sato T (2004) Chemotherapy in the treatment of advanced gallbladder cancer. Oncology 66:138–142PubMedCrossRefGoogle Scholar
  31. 31.
    Sikora SS, Singh RK (2006) Surgical strategies in patients with gallbladder cancer: Nihilism to optimism. J Surg Oncol 93:670–681PubMedCrossRefGoogle Scholar
  32. 32.
    Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, Raina V, Shukla NK, Thulkar S, Garg P, Chaudhary SP (2010) Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol 28:4581–4586. doi:10.1200/jco.2010.29.3605 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Seung Woo Yi
    • 1
  • Dae Ryong Kang
    • 2
  • Kyung Sik Kim
    • 3
  • Mi Suk Park
    • 4
  • Jinsil Seong
    • 5
  • Jeong Youp Park
    • 1
  • Seung Min Bang
    • 1
  • Si Young Song
    • 1
  • Jae Bock Chung
    • 1
  • Seung Woo Park
    • 1
  1. 1.Department of Internal Medicine, Institute of GastroenterologyYonsei University College of MedicineSeoulRepublic of Korea
  2. 2.Biostatistics Collaboration UnitYonsei University College of MedicineSeoulRepublic of Korea
  3. 3.Department of SurgeryYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Department of Diagnostic RadiologyYonsei University College of MedicineSeoulRepublic of Korea
  5. 5.Department of Radiation OncologyYonsei University College of MedicineSeoulRepublic of Korea

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