Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Two-Week Combination Chemotherapy with Gemcitabine, High-Dose Folinic Acid and 5 Fluorouracil (GEMFUFOL) as First-Line Treatment of Metastatic Biliary Tract Cancers

  • Unal, Olcun Umit (Department of Medical Oncology, Medical Faculty, Ataturk University) ;
  • Oztop, Ilhan (Department of Medical Oncology, Medical Faculty, Dokuz Eylul University) ;
  • Unek, Ilkay Tugba (Department of Medical Oncology, Tepecik Education and Research Hospital) ;
  • Yilmaz, Ahmet Ugur (Department of Medical Oncology, Medical Faculty, Izmir University)
  • Published : 2013.09.30
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Abstract

Background: The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouracil and leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer. Materials and Methods: All patients received folinic acid $400mg/m^2$ on day 1, 5-fluorouracil bolus $400mg/m^2$ on day 1, IV infusion of 5-fluorouracil $2400mg/m^2$ over 46 hours, and gemcitabine $1250mg/m^2$ on day 1. Results: A total of 29 patients with metastatic biliary tract cancer received GEMFUFOL regimen as the firstline treatment. The mean follow-up was 22.1 months (95%CI, 12.5-31.8). One patient (3.4%) achieved complete response, 5 (17.2%) had partial response, and 4 (13.8%) had stable disease. The median progression-free survival was 3.3 months (95%CI, 2.9-3.7), and the median overall survival was 8.8 months (95%CI, 3.5-14). The 1-year and 2-year survival rates were 58.6% and 30%, respectively. Grade 3 and 4 toxicity included neutropenia in 4 patients (13.7%), thrombocytopenia in 2 (6.8%), anemia2 (6.8%), and alopecia in 1 (3.4%). Two patients (6.8%) developed febrile neutropenia. A dose reduction was achieved in 8 patients (27.6%) while 5 patients had extended-interval dosage (17.2%) for toxicity. Conclusions: The GEMFUFOL chemotherapy regimen was generally efficacious and tolerable as a first-line treatment of metastatic biliary tract cancer.

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References

  1. Chen JS, Jan YY, Lin YC, et al (1998). Weekly 24 h infusion of high-dose 5-fluorouracil and leucovorin in patients with biliary tract carcinomas. Anticancer Drugs, 5, 393-7.
  2. Cho JY, Paik YH, Chang YS, et al (2005). Capecitabine combined with gemcitabine (CapGem) as first-line treatment in patients with advanced/metastatic biliary tract carcinoma. Cancer, 104, 2753-8. https://doi.org/10.1002/cncr.21591
  3. Croitoru A, Gramaticu I, Dinu I, et al (2012). Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in locally advanced and metastatic biliary tract carcinoma - a retrospective study. J Gastrointestin Liver Dis, 21, 277-84.
  4. Cunningham D, Chau I, Stocken DD, et al (2005). Phase III randomized comparison of gemcitabine (gem) vs gemcitabine plus capecitabine (Gem-CAP) in patients with advanced pancreatic cancer. Eur J Cancer, 3, 11.
  5. Ducreux M, Van Cutsem E, Van Laethem JL, et al (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. https://doi.org/10.1016/j.ejca.2004.10.026
  6. Eckel F, Schmid RM (2007). Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer, 6, 896-902.
  7. Falkson G, MacIntyre JM, Moertel CG (1984). Eastern Cooperative Oncology Group experience with chemotherapy for inoperable gallbladder and bile duct cancer. Cancer, 54, 965. https://doi.org/10.1002/1097-0142(19840915)54:6<965::AID-CNCR2820540603>3.0.CO;2-X
  8. Gebbia V, Majello E, Testa A, et al (1996). Treatment of advanced adenocarcinomas of the exocrine pancreas and the gallbladder with 5-fluorouracil, high dose levofolinic acid and oral hydroxyurea on a weekly schedule. Results of a multicenter study of the Southern Italy Oncology Group (G.O.I.M.). Cancer, 78, 1300-7. https://doi.org/10.1002/(SICI)1097-0142(19960915)78:6<1300::AID-CNCR19>3.0.CO;2-4
  9. Gesto DS, Cerqueira NM, Fernandes PA, et al(2012). Gemcitabine: a critical nucleoside for cancer therapy. Curr Med Chem, 19, 1076-87. https://doi.org/10.2174/092986712799320682
  10. Glimelius B, Hoffman K, Sjoden PO, et al (1996). Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol, 7, 593-600. https://doi.org/10.1093/oxfordjournals.annonc.a010676
  11. Hamdani NH, Qadri SK, Aggarwalla R, et al (2012). Clinicopathological study of gall bladder carcinoma with special reference to gallstones: our 8-year experience from eastern India. Asian Pac J Cancer Prev, 13, 5613-7. https://doi.org/10.7314/APJCP.2012.13.11.5613
  12. Harvey JH, Smith FP, Schein PS (1984). 5-Fluorouracil, mitomycin, and doxorubicin (FAM) in carcinoma of the biliary tract. J Clin Oncol, 2, 1245-8. https://doi.org/10.1200/JCO.1984.2.11.1245
  13. Iqbal S, Rankin C, Lenz HJ, et al (2011). A phase II trial of gemcitabine and capecitabine in patients with unresectable or metastatic gallbladder cancer or cholangiocarcinoma: Southwest Oncology Group study S0202. Cancer Chemother Pharmacol, 6, 1595-602.
  14. Kajanti M, Pyrhonen S (1994). Epirubicin-sequential methotrexate-5-fluorouracil-leucovorin treatment in advanced cancer of the extrahepatic biliary system. A phase II study. Am J Clin Oncol, 17, 223. https://doi.org/10.1097/00000421-199406000-00008
  15. Kanai M, Yoshimura K, Tsumura T, et al (2011). A multiinstitution phase II study of gemcitabine/S-1 combination chemotherapy for patients with advanced biliary tract cancer. Cancer Chemother Pharmacol, 67, 1429-34. https://doi.org/10.1007/s00280-010-1443-5
  16. Kameda R, Ando T, Kobayashi S, et al (2013). A retrospective study of chemotherapy with cisplatin plus gemcitabine after the failure of gemcitabine monotherapy for biliary tract cancer. Jpn J Clin Oncol, 6, 636-40.
  17. Kim JY, Kim YJ, Lee KW, et al (2013). Practical outcome of adjuvant FOLFOX4 chemotherapy in elderly patients with stage III colon cancer: single-center study in Korea. Jpn J Clin Oncol, 43,132-8. https://doi.org/10.1093/jjco/hys195
  18. Lim KH, Han SW, Oh DY, et al (2012). Outcome of infusional 5-fluorouracil, doxorubicin, and mitomycin-C (iFAM) chemotherapy and analysis of prognostic factors in patients with refractory advanced biliary tract cancer. Oncol, 83, 57-66. https://doi.org/10.1159/000338795
  19. Louvet C, Andre T, Hammel P (2001). Phase II trial of bimonthly leucovorin, 5-fluorouracil and gemcitabine for advanced pancreatic adenocarcinoma (FOLFUGEM). Ann Oncol, 12, 675-9. https://doi.org/10.1023/A:1011139808426
  20. Okusaka T, Nakachi K, Fukutomi A, et al (2010). Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer, 10, 469-74.
  21. Oztop I, Yilmaz U, Yavuzsen T, et al (2004). Gemcitabine combined with infusional 5-Fluorouracil and High-Dose leucovorin for the treatment of advanced carcinoma of the pancreas. Chemotherapy, 50, 127-32. https://doi.org/10.1159/000077886
  22. Park JS, Oh SY, Kim SH, et al (2005). Single-agent gemcitabine in the treatment of advanced biliary tract cancers: a phase II study. Jpn J Clin Oncol, 35, 68-73. https://doi.org/10.1093/jjco/hyi021
  23. Qu K, Liu SN, Chang HL, et al (2012). Gallbladder cancer: a subtype of biliary tract cancer which is a current challenge in China. Asian Pac J Cancer Prev, 13, 1317-20. https://doi.org/10.7314/APJCP.2012.13.4.1317
  24. Santini D, Virzi V, Vasile E, et al (2012). A phase II trial of fixed-dose rate gemcitabine plus capecitabine in metastatic/ advanced biliary tract cancer patients. Oncology, 82, 75-82. https://doi.org/10.1159/000329079
  25. Sasaki T, Isayama H, Nakai Y, et al (2010). Multicenter, phase II study of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer. Cancer Chemother Pharmacol, 65, 1101-7. https://doi.org/10.1007/s00280-009-1115-5
  26. Sasaki T, Isayama H, Nakai Y, et al (2011). Feasibility study of gemcitabine and cisplatin combination chemotherapy for patients with refractory biliary tract cancer. Invest New Drugs, 6, 1488-93.
  27. Sharma A, Dwary AD, Mohanti BK, et al (2010). Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol, 28, 4581-6. https://doi.org/10.1200/JCO.2010.29.3605
  28. Suzuki E, Furuse J, Ikeda M, et al (2010). Treatment efficacy/ safety and prognostic factors in patients with advanced biliary tract cancer receiving gemcitabine monotherapy: an analysis of 100 cases. Oncol, 79, 39-45. https://doi.org/10.1159/000318020
  29. Tan JW, Hu BS, Chu YJ, et al (2013). One-stage resection for bismuth type IV hilar cholangiocarcinoma with high hilar resection and parenchyma-preserving strategies: a cohort study. World J Surg, 3, 614-21.
  30. Valle JW, Wasan H, Johnson P, et al (2009). 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, 101, 621-7. https://doi.org/10.1038/sj.bjc.6605211
  31. Valle J, Wasan H, Palmer DH, et al (2010). Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med, 362, 1273-81. https://doi.org/10.1056/NEJMoa0908721
  32. Wagner AD, Buechner-Steudel P, Moehler M, et al (2009). Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials. Br J Cancer, 101,1846-52. https://doi.org/10.1038/sj.bjc.6605377
  33. Yonemoto N, Furuse J, Okusaka T, et al (2007). A multi-center retrospective analysis of survival benefits of chemotherapy for unresectable biliary tract cancer. Jpn J Clin Oncol, 37, 843-51. https://doi.org/10.1093/jjco/hym116

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