Skip to main content

Advertisement

SpringerLink
Log in

A phase II study of gemcitabine in combination with oxaliplatin as first-line chemotherapy in patients with inoperable biliary tract cancer

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study is to investigate the efficacy and safety of gemcitabine and oxaliplatin combination chemotherapy as first-line therapy in patients with inoperable biliary tract cancer (BTC).

Methods

The treatment of this non-randomized phase II study consisted of gemcitabine 1,000 mg/m2 intravenously (i.v.) on day 1 and oxaliplatin 85 mg/m2 i.v. on day 2 every 2 weeks until disease progression, unaccep toxicity or patients’ refusal.

Results

From Sept 2006 to Oct 2007, 40 patients were enrolled. In the ITT analysis, the objective response rate was 15.0% and the disease control rate was 52.5%. The median overall survival (95% CI) was 8.5 months (6.4–10.7) and the time to progression was 4.2 months (0.5–7.9). For the 305 cycles, observed grade 3/4 toxicity was uncommon.

Conclusions

Gemcitabine and dose adjusted oxaliplatin combination chemotherapy had moderate anti-tumor activity and was well tolerated as a first-line treatment for patients with inoperable BTC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Shin HR, Jung KW, Won YJ, Park JG (2004) 2002 annual report of the Korea central cancer registry: based on registered data from 139 hospitals. Cancer Res Treat 36:103–114

    Article  PubMed  Google Scholar 

  2. Bartlett DL, Ramanathan RK, Deutsch M (2005) Cancer of the biliary tree. In: DeVita VT, Hellman S, Rosenberg SA (eds) CANCER principle and practice of oncology, 7th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1009–1035

    Google Scholar 

  3. Glimelius B, Hoffman K, Sjödén PO et al (1996) Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol 7:593–600

    PubMed  CAS  Google Scholar 

  4. Patt YZ, Jones DV Jr, Hoque A et al (1996) Phase II trail of intravenous fluorouracil and subcutaneous interferon alfa-2b for biliary tract cancer. J Clin Oncol 14:2311–2315

    PubMed  CAS  Google Scholar 

  5. Choi CW, Choi IK, Seo JH et al (2000) Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas. Am J Clin Oncol 23:425–428

    Article  PubMed  CAS  Google Scholar 

  6. 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

    Article  PubMed  CAS  Google Scholar 

  7. Ducreux M, Rougier P, Fandi A et al (1998) Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin. Ann Oncol 9:653–656

    Article  PubMed  CAS  Google Scholar 

  8. Penz M, Kornek GV, Raderer MU et al (2001) Phase II trial of two-weekly gemcitabine in patients with advanced biliary tract cancer. Ann Oncol 12:183–186

    Article  PubMed  CAS  Google Scholar 

  9. Gallardo JO, Rubio B, Fodor M et al (2001) A phase II study of gemcitabine in gallbladder carcinoma. Ann Oncol 12:1403–1406

    Article  PubMed  CAS  Google Scholar 

  10. Harder J, Riecken B, Kummer O et al (2006) Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer. Br J Cancer 95:848–852

    Article  PubMed  CAS  Google Scholar 

  11. Kim ST, Park JO, Lee J et al (2006) A phase II study of gemcitabine and cisplatin in advanced biliary tract cancer. Cancer 106:1339–1346

    Article  PubMed  CAS  Google Scholar 

  12. Park BK, Kim YJ, Park JY et al (2006) Phase II study of gemcitabine and cisplatin in advanced biliary tract cancer. J Gastroenterol Hepatol 21:999–1003

    Article  PubMed  CAS  Google Scholar 

  13. Murad AM, Guimaraes RC, Aragao BC et al (2003) Phase II trial of the use of gemcitabine and 5-fluorouracil in the treatment of advanced pancreatic and biliary tract cancer. Am J Clin Oncol 26:151–154

    Article  PubMed  CAS  Google Scholar 

  14. Lee J, Kim TY, Lee MA et al (2008) Phase II trial of gemcitabine combined with cisplatin in patients with inoperable biliary tract carcinomas. Cancer Chemother Pharmacol 61:47–52

    Article  PubMed  CAS  Google Scholar 

  15. Faivre S, Raymond E, Woynarowski JM, Cvitkovic E (1999) Suppraadditive effect of 2′, 2′- difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines. Cancer Chemother Pharmacol 44:117–123

    Article  PubMed  CAS  Google Scholar 

  16. André T, Tournigand C, Rosmorduc O et al (2004) Gemcitabine and combined with oxliplatin (GEMOX) in advanced biliary tract adenocarcinoma: a GERCOR study. Ann Oncol 15:1339–1343

    Article  PubMed  Google Scholar 

  17. Louvet C, André T, Lledo G et al (2002) Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol 20:1512–1518

    Article  PubMed  CAS  Google Scholar 

  18. Airoldi M, Cattel L, Passera R, Pedani F, Milla P, Zanon C (2006) Gemcitabine and oxaliplatin in patients with pancreatic adenocarcinoma: clinical and pharmacokinetic data. Pancreas 32:44–50

    Article  PubMed  CAS  Google Scholar 

  19. Louvet C, Labianca R, Hammel P et al (2005) Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 23:3509–3516

    Article  PubMed  CAS  Google Scholar 

  20. Eklund JW, Trifilio S, Mulcahy MF (2005) Chemotherapy dosing in the setting of liver dysfunction. Oncology (Williston Park) 19:1057–1063

    Google Scholar 

  21. Tempero M, Plunkett W, Ruiz Van Haperen V et al (2003) Randomized phase II comparison of dose-intense gemcitabine: Thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 21:3402–3408

    Article  PubMed  CAS  Google Scholar 

  22. Abbruzzese JL, Grunewald R, Weeks EA et al (1991) A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. J Clin Oncol 9:491–498

    PubMed  CAS  Google Scholar 

  23. Guan Z, Wang Y, Maoleekoonpairoj S et al (2003) Prospective randomised phase II study of gemcitabine at standard or fixed dose rate schedule in unresectable hepatocellular carcinoma. Br J Cancer 89:1865–1869

    Article  PubMed  CAS  Google Scholar 

  24. Gridelli C, Gallo C, Ceribelli A et al (2007) Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC(GECO) study. Lancet Oncol 8:500–512

    Article  PubMed  CAS  Google Scholar 

  25. Taïeb J, Bonyhay L, Golli L et al (2003) Gemcitabine plus oxaliplatin for patients with advanced hepatocellular carcinoma using two different schedules. Cancer 98:2664–2670

    Article  PubMed  CAS  Google Scholar 

  26. Eckel F, Schmid RM (2007) Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer 96:896–902

    Article  PubMed  CAS  Google Scholar 

  27. 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 37:843–851

    Article  PubMed  Google Scholar 

  28. Doval DC, Sekhon JS, Gupta SK et al (2004) A phase II study of gemcitabine and cisplatin in chemotherapy-naive, unresectable gall bladder cancer. Br J Cancer 90:1516–1520

    Article  PubMed  CAS  Google Scholar 

  29. Knox JJ, Hedley D, Oza A et al (2005) Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol 23:2332–2338

    Article  PubMed  CAS  Google Scholar 

  30. André T, Reyes-Vidal JM, Fartoux L et al (2008) Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: a phase II study. Br J Cancer 99:862–867

    Article  PubMed  CAS  Google Scholar 

  31. Fink D, Aebi S, Howell SB (1998) The role of DNA mismatch repair in drug resistance. Clin Cancer Res 4:1–6

    PubMed  CAS  Google Scholar 

  32. Kohya N, Kitajima Y, Kitahara K, Miyazaki K (2003) Mutation analysis of K-ras and beta-catenin genes related to O6-methylguanin-DNA methyltransferase and mismatch repair protein status in human gallbladder carcinoma. Int J Mol Med 11:65–69

    PubMed  CAS  Google Scholar 

  33. Adlard JW, Richman SD, Seymour MT, Quirke P (2002) Prediction of the response of colorectal cancer to systemic therapy. Lancet Oncol 3:75–82

    Article  PubMed  CAS  Google Scholar 

  34. van Ruiz Haperen VW, Veerman G, Eriksson S et al (1994) Development and molecular characterization of a 2′, 2′-difluorodeoxycytidine-resistant variant of the human ovarian carcinoma cell line A2780. Cancer Res 54:4138–4143

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon Hospital, 1174, Jung-Dong, Wonmi-Gu, Bucheon-Si, Gyeonggi-Do, 420-853, South Korea

    Hyun Jung Kim, Chan Kyu Kim, Sung Kyu Park & Dae Sik Hong

  2. Division of Gastroenterology, Soonchunhyang University College of Medicine, Bucheon, Republic of Korea

    Young Seok Kim & Jong Ho Moon

  3. Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Republic of Korea

    Nam Su Lee, Sang-Cheol Lee, Jong-Ho Won & Hee Sook Park

  4. Division of Gastroenterology, Soonchunhyang University College of Medicine, Seoul, Republic of Korea

    Young Gook Cheon & Young Deok Cho

  5. Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea

    Sang Byung Bae & Kyu Taek Lee

  6. Division of Gastroenterology, Soonchunhyang University College of Medicine, Cheonan, Republic of Korea

    Sang Heum Park

Authors
  1. Hyun Jung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nam Su Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sang-Cheol Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sang Byung Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chan Kyu Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Young Gook Cheon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Young Seok Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jong Ho Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Young Deok Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sang Heum Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kyu Taek Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sung Kyu Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jong-Ho Won
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Hee Sook Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Dae Sik Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dae Sik Hong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, H.J., Lee, N.S., 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 64, 371–377 (2009). https://doi.org/10.1007/s00280-008-0883-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-008-0883-7

Keywords

Search

Navigation