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Current status of chemotherapy for the treatment of advanced biliary tract cancer

  • Sasaki, Takashi (Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo) ;
  • Isayama, Hiroyuki (Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo) ;
  • Nakai, Yousuke (Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo) ;
  • Koike, Kazuhiko (Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo)
  • Received : 2013.04.18
  • Accepted : 2013.05.09
  • Published : 2013.09.01

Abstract

Chemotherapy is indispensable for the treatment of advanced biliary tract cancer. Recently, reports regarding first-line chemotherapy have increased, and first-line chemotherapy treatment has become gradually more sophisticated. Gemcitabine and cisplatin combination therapy (or gemcitabine and oxaliplatin combination therapy) have become the standard of care for advanced biliary tract cancer. Oral f luoropyrimidines have also been shown to have good antitumor effects. Gemcitabine, platinum compounds, and oral fluoropyrimidines are now considered key drugs for the treatment of advanced biliary tract cancer. Several clinical trials using molecular targeted agents are also ongoing. Combination therapy using cytotoxic agents and molecular-targeted agents has been evaluated widely. However, reports regarding second-line chemotherapy remain limited, and it has not yet been clarified whether second-line chemotherapy can improve the prognosis of advanced biliary tract cancer. Thus, there is an urgent need to establish secondline standard chemotherapy treatment for advanced biliary tract cancer. Several problems exist when assessing the results of previous reports concerning advanced biliary tract cancer. In the present review, the current status of the treatment of advanced biliary tract cancer is summarized, and several associated problems are indicated. These problems should be solved to achieve more sophisticated treatment of advanced biliary tract cancer.

Keywords

References

  1. Randi G, Malvezzi M, Levi F, et al. Epidemiology of biliary tract cancers: an update. Ann Oncol 2009;20:146-159.
  2. Center for Cancer Control and Information Services, National Cancer Center. Vital statistics [Internet]. Tokyo (JP): National Cancer Center, c2010 [cited 2013 Apr 18]. Available from: http://ganjoho.jp/professional/statistics/ statistics.html.
  3. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30. https://doi.org/10.3322/caac.21166
  4. Jung KW, Park S, Won YJ, et al. Prediction of cancer incidence and mortality in Korea, 2012. Cancer Res Treat 2012;44:25-31. https://doi.org/10.4143/crt.2012.44.1.25
  5. Khan SA, Taylor-Robinson SD, Toledano MB, Beck A, Elliott P, Thomas HC. Changing international trends in mortality rates for liver, biliary and pancreatic tumours. J Hepatol 2002;37:806-813. https://doi.org/10.1016/S0168-8278(02)00297-0
  6. Hezel AF, Zhu AX. Systemic therapy for biliary tract cancers. Oncologist 2008;13:415-423. https://doi.org/10.1634/theoncologist.2007-0252
  7. Miyakawa S, Ishihara S, Horiguchi A, Takada T, Miyazaki M, Nagakawa T. Biliary tract cancer treatment:5,584 results from the Biliary Tract Cancer Statistics Registry from 1998 to 2004 in Japan. J Hepatobiliary Pancreat Surg 2009;16:1-7. https://doi.org/10.1007/s00534-008-0015-0
  8. Sasaki T, Isayama H, Nakai Y, et al. Improvement of prognosis for unresectable biliary tract cancer. World J Gastroenterol 2013;19:72-77. https://doi.org/10.3748/wjg.v19.i1.72
  9. Tada M, Nakai Y, Sasaki T, et al. Recent progress and limitations of chemotherapy for pancreatic and biliary tract cancers. World J Clin Oncol 2011;2:158-163. https://doi.org/10.5306/wjco.v2.i3.158
  10. Glimelius B, Hoffman K, Sjoden PO, et al. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol 1996;7:593-600. https://doi.org/10.1093/oxfordjournals.annonc.a010676
  11. Takada T, Nimura Y, Katoh H, et al. Prospective randomized trial of 5-f luorouracil, doxorubicin, and mitomycin C for non-resectable pancreatic and biliary carcinoma: multicenter randomized trial. Hepatogastroenterology 1998;45:2020-2026.
  12. Sharma A, Dwary AD, Mohanti BK, et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol 2010;28:4581-4586. https://doi.org/10.1200/JCO.2010.29.3605
  13. Eckel F, Schmid RM. Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer 2007;96:896-902. https://doi.org/10.1038/sj.bjc.6603648
  14. Yonemoto N, Furuse J, Okusaka T, et al. A multi-center retrospective analysis of survival benefits of chemotherapy for unresectable biliary tract cancer. Jpn J Clin Oncol 2007;37:843-851. https://doi.org/10.1093/jjco/hym116
  15. Doval DC, Sekhon JS, Gupta SK, et al. A phase II study of gemcitabine and cisplatin in chemotherapynaive, unresectable gall bladder cancer. Br J Cancer 2004;90:1516-1520. https://doi.org/10.1038/sj.bjc.6601736
  16. Thongprasert S, Napapan S, Charoentum C, Moonprakan S. Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. Ann Oncol 2005;16:279-281. https://doi.org/10.1093/annonc/mdi046
  17. Kim ST, Park JO, Lee J, et al. A Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer. Cancer 2006;106:1339-1346. https://doi.org/10.1002/cncr.21741
  18. Valle JW, Wasan H, Johnson P, et al. Gemcitabine alone or in combination with cisplatin in patients with advanced or metastatic cholangiocarcinomas or other biliary tract tumours: a multicentre randomised phase II study: The UK ABC-01 Study. Br J Cancer 2009;101:621- 627. https://doi.org/10.1038/sj.bjc.6605211
  19. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010;362:1273-1281. https://doi.org/10.1056/NEJMoa0908721
  20. Okusaka T, Nakachi K, Fukutomi 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;103:469-474. https://doi.org/10.1038/sj.bjc.6605779
  21. Andre T, Tournigand C, Rosmorduc O, et al. Gemcitabine combined with oxaliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study. Ann Oncol 2004;15:1339-1343. https://doi.org/10.1093/annonc/mdh351
  22. Harder J, Riecken B, Kummer O, et al. Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer. Br J Cancer 2006;95:848-852. https://doi.org/10.1038/sj.bjc.6603334
  23. Andre T, Reyes-Vidal JM, Fartoux L, et al. Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: a phase II study. Br J Cancer 2008;99:862-867. https://doi.org/10.1038/sj.bjc.6604628
  24. Kim HJ, Lee NS, Lee SC, et al. A phase II study of gemcitabine in combination with oxaliplatin as first-line chemotherapy in patients with inoperable biliary tract cancer. Cancer Chemother Pharmacol 2009;64:371-377. https://doi.org/10.1007/s00280-008-0883-7
  25. Jang JS, Lim HY, Hwang IG, et al. Gemcitabine and oxaliplatin in patients with unresectable biliary cancer including gall bladder cancer: a Korean Cancer Study Group phase II trial. Cancer Chemother Pharmacol 2010;65:641-647. https://doi.org/10.1007/s00280-009-1069-7
  26. Cho JY, Paik YH, Chang YS, et al. Capecitabine combined with gemcitabine (CapGem) as first-line treatment in patients with advanced/metastatic biliary tract carcinoma. Cancer 2005;104:2753-2758. https://doi.org/10.1002/cncr.21591
  27. Knox JJ, Hedley D, Oza A, et al. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol 2005;23:2332-2338. https://doi.org/10.1200/JCO.2005.51.008
  28. Riechelmann RP, Townsley CA, Chin SN, Pond GR, Knox JJ. Expanded phase II trial of gemcitabine and capecitabine for advanced biliary cancer. Cancer 2007;110:1307-1312. https://doi.org/10.1002/cncr.22902
  29. Koeberle D, Saletti P, Borner M, et al. Patient-reported outcomes of patients with advanced biliary tract cancers receiving gemcitabine plus capecitabine: a multicenter, phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol 2008;26:3702-3708. https://doi.org/10.1200/JCO.2008.16.5704
  30. Ueno H, Okusaka T, Ikeda M, Takezako Y, Morizane C. Phase II study of S-1 in patients with advanced biliary tract cancer. Br J Cancer 2004;91:1769-1774. https://doi.org/10.1038/sj.bjc.6602208
  31. Furuse J, Okusaka T, Boku N, et al. S-1 monotherapy as first-line treatment in patients with advanced biliary tract cancer: a multicenter phase II study. Cancer Chemother Pharmacol 2008;62:849-855. https://doi.org/10.1007/s00280-007-0673-7
  32. Sasaki T, Isayama H, Yashima Y, et al. S-1 monotherapy in patients with advanced biliary tract cancer. Oncology 2009;77:71-74. https://doi.org/10.1159/000226214
  33. Sasaki T, Isayama H, Nakai Y, et al. Multicenter, phase II study of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer. Cancer Chemother Pharmacol 2010;65:1101-1107. https://doi.org/10.1007/s00280-009-1115-5
  34. Kanai M, Yoshimura K, Tsumura T, et al. A multi-institution phase II study of gemcitabine/S-1 combination chemotherapy for patients with advanced biliary tract cancer. Cancer Chemother Pharmacol 2011;67:1429-1434. https://doi.org/10.1007/s00280-010-1443-5
  35. Sasaki T, Isayama H, Nakai Y, et al. A randomized phase II study of gemcitabine and S-1 combination therapy versus gemcitabine monotherapy for advanced biliary tract cancer. Cancer Chemother Pharmacol 2013;71:973-979. https://doi.org/10.1007/s00280-013-2090-4
  36. Morizane C, Okusaka T, Mizusawa J, et al. Randomized phase II trial of gemcitabine plus S-1 combination therapy versus S-1 in advanced biliary tract cancer: results of the Japan Clinical Oncology Group study (JCOG0805) [abstract]. J Clin Oncol 2012;30(4 Suppl):abstr 255.
  37. Kim YJ, Im SA, Kim HG, et al. A phase II trial of S-1 and cisplatin in patients with metastatic or relapsed biliary tract cancer. Ann Oncol 2008;19:99-103. https://doi.org/10.1093/annonc/mdn320
  38. Kang MJ, Lee JL, Kim TW, et al. Randomized phase II trial of S-1 and cisplatin versus gemcitabine and cisplatin in patients with advanced biliary tract adenocarcinoma. Acta Oncol 2012;51:860-866. https://doi.org/10.3109/0284186X.2012.682628
  39. Kim TW, Chang HM, Kang HJ, et al. Phase II study of capecitabine plus cisplatin as first-line chemotherapy in advanced biliary cancer. Ann Oncol 2003;14:1115-1120. https://doi.org/10.1093/annonc/mdg281
  40. Hong YS, Lee J, Lee SC, et al. Phase II study of capecitabine and cisplatin in previously untreated advanced biliary tract cancer. Cancer Chemother Pharmacol 2007;60:321-328. https://doi.org/10.1007/s00280-006-0380-9
  41. Sanz-Altamira PM, O'Reilly E, Stuart KE, et al. A phase II trial of irinotecan (CPT-11) for unresectable biliary tree carcinoma. Ann Oncol 2001;12:501-504. https://doi.org/10.1023/A:1011135014895
  42. Alberts SR, Fishkin PA, Burgart LJ, et al. CPT-11 for bile-duct and gallbladder carcinoma: a phase II North Central Cancer Treatment Group (NCCTG) study. Int J Gastrointest Cancer 2002;32:107-114. https://doi.org/10.1385/IJGC:32:2-3:107
  43. Jones DV Jr, Lozano R, Hoque A, Markowitz A, Patt YZ. Phase II study of paclitaxel therapy for unresectable biliary tree carcinomas. J Clin Oncol 1996;14:2306-2310. https://doi.org/10.1200/JCO.1996.14.8.2306
  44. Papakostas P, Kouroussis C, Androulakis N, et al. Firstline chemotherapy with docetaxel for unresectable or metastatic carcinoma of the biliary tract: a multicentre phase II study. Eur J Cancer 2001;37:1833-1838. https://doi.org/10.1016/S0959-8049(01)00214-3
  45. Philip PA, Mahoney MR, Allmer C, et al. Phase II study of erlotinib in patients with advanced biliary cancer. J Clin Oncol 2006;24:3069-3074. https://doi.org/10.1200/JCO.2005.05.3579
  46. Ramanathan RK, Belani CP, Singh DA, et al. A phase II study of lapatinib in patients with advanced biliary tree and hepatocellular cancer. Cancer Chemother Pharmacol 2009;64:777-783. https://doi.org/10.1007/s00280-009-0927-7
  47. Bengala C, Bertolini F, Malavasi N, et al. Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial. Br J Cancer 2010;102:68-72. https://doi.org/10.1038/sj.bjc.6605458
  48. El-Khoueiry AB, Rankin CJ, Ben-Josef E, et al. SWOG 0514: a phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma. Invest New Drugs 2012;30:1646-1651. https://doi.org/10.1007/s10637-011-9719-0
  49. Bekaii-Saab T, Phelps MA, Li X, et al. Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers. J Clin Oncol 2011;29:2357-2363. https://doi.org/10.1200/JCO.2010.33.9473
  50. Lubner SJ, Mahoney MR, Kolesar JL, 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;28:3491-3497. https://doi.org/10.1200/JCO.2010.28.4075
  51. El-Khoueiry AB, Rankin C, Iqbal S, et al. SWOG 0941: a phase II study of sorafenib and erlotinib in patients (pts) with advanced gallbladder cancer or cholangiocarcinoma [abstract]. J Clin Oncol 2012;30(15 Suppl):abstr 4113.
  52. Gruenberger B, Schueller J, Heubrandtner U, et al. Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study. Lancet Oncol 2010;11:1142-1148. https://doi.org/10.1016/S1470-2045(10)70247-3
  53. Malka D, Fartoux L, Rousseau V, et al. Gemcitabine and oxaliplatin (GEMOX) alone or in combination with cetuximab as first-line treatment for advanced biliary cancer: final analysis of a randomized phase II trial (BINGO) [abstract]. J Clin Oncol 2012;30(15 Suppl):abstr 4032.
  54. Lee J, Park SH, Chang HM, et al. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliarytract cancer: a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2012;13:181-188. https://doi.org/10.1016/S1470-2045(11)70301-1
  55. Zhu AX, Meyerhardt JA, Blaszkowsky LS, et al. Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study. Lancet Oncol 2010;11:48-54. https://doi.org/10.1016/S1470-2045(09)70333-X
  56. Walter T, Horgan AM, McNamara M, et al. Feasibility and benefits of second-line chemotherapy in advanced biliary tract cancer: a large retrospective study. Eur J Cancer 2013;49:329-335. https://doi.org/10.1016/j.ejca.2012.08.003
  57. Lee MA, Woo IS, Kang JH, Hong YS, Lee KS. Gemcitabine and cisplatin combination chemotherapy in intrahepatic cholangiocarcinoma as second-line treatment: report of four cases. Jpn J Clin Oncol 2004;34:547-550.
  58. Sasaki T, Isayama H, Nakai Y, et al. Feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with refractory biliary tract cancer. Invest New Drugs 2011;29:1488-1493. https://doi.org/10.1007/s10637-010-9485-4
  59. Paule B, Herelle MO, Rage E, et al. Cetuximab plus gemcitabine-oxaliplatin (GEMOX) in patients with refractory advanced intrahepatic cholangiocarcinomas. Oncology 2007;72:105-110. https://doi.org/10.1159/000111117
  60. Oh SY, Jeong CY, Hong SC, et al. Phase II study of second line gemcitabine single chemotherapy for biliary tract cancer patients with 5-fluorouracil refractoriness. Invest New Drugs 2011;29:1066-1072. https://doi.org/10.1007/s10637-010-9417-3
  61. Suzuki E, Ikeda M, Okusaka T, et al. A multicenter phase II of S-1 in gemcitabine-refractory biliary tract cancer [abstract]. J Clin Oncol 2010;28(15 Suppl):abstr 4145.
  62. Sasaki T, Isayama H, Nakai Y, et al. Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine. Invest New Drugs 2012;30:708-713. https://doi.org/10.1007/s10637-010-9553-9
  63. Lim KH, Han SW, Oh DY, Im SA, Kim TY, Bang YJ. Outcome of infusional 5-fluorouracil, doxorubicin, and mitomycin-C (iFAM) chemotherapy and analysis of prognostic factors in patients with refractory advanced biliary tract cancer. Oncology 2012;83:57-66. https://doi.org/10.1159/000338795
  64. Roth A, Schleyer E, Schoppmeyer K, et al. Imatinib mesylate for palliative second-line treatment of advanced biliary tract cancer: a bicentric phase II study. Onkologie 2011;34:469-470. https://doi.org/10.1159/000331065
  65. Yi JH, Thongprasert S, Lee J, et al. A phase II study of sunitinib as a second-line treatment in advanced biliary tract carcinoma: a multicentre, multinational study. Eur J Cancer 2012;48:196-201. https://doi.org/10.1016/j.ejca.2011.11.017
  66. Katayose Y, Ohtsuka H, Kitamura Y, et al. An analysis of a second-line S-1 monotherapy for gemcitabinerefractory biliary tract cancer. Hepatogastroenterology 2012;59:691-695.
  67. Kobayashi S, Ueno M, Ohkawa S, et al. A retrospective study of S-1 monotherapy as second-line treatment for patients with advanced biliary tract cancer. Jpn J Clin Oncol 2012;42:800-806. https://doi.org/10.1093/jjco/hys102
  68. Sasaki T, Isayama H, Nakai Y, et al. A retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer [abstract]. J Clin Oncol 2013;31(4 Suppl):abstr 258.
  69. Tempero MA, Arnoletti JP, Behrman SW, et al. Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2012;10:703-713. https://doi.org/10.6004/jnccn.2012.0073
  70. Sasaki T, Isayama H, Ito Y, et al. Comparing the treatment outcomes between unresectable and recurrent cases receiving gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer: pooled analysis of two prospective studies [abstract]. J Clin Oncol 2012;30(4 Suppl):abstr 331.
  71. Hezel AF, Deshpande V, Zhu AX. Genetics of biliary tract cancers and emerging targeted therapies. J Clin Oncol 2010;28:3531-3540. https://doi.org/10.1200/JCO.2009.27.4787
  72. Sasaki T, Isayama H, Nakai Y, et al. Prognostic factors in patients with advanced biliary tract cancer receiving chemotherapy. Cancer Chemother Pharmacol 2011;67:847-853. https://doi.org/10.1007/s00280-010-1360-7

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