Phase II study of 5-fluorouracil and paclitaxel in patients with gemcitabine-refractory pancreatic cancer



There is no effective salvage regimen for failed gemcitabine-based chemotherapy. This study evaluated the efficacy and toxicity of 5-fluorouracil and paclitaxel in patients with gemcitabine-refractory pancreatic cancer.


Between January 2004 and December 2007, 28 patients with pancreatic cancer previously treated with gemcitabine-based chemotherapy were enrolled. 5-Fluorouracil 1,000 mg/m2 was infused (days 1, 2, and 3) and paclitaxel 175 mg/m2 (day 1) was administered every 4 weeks. The primary endpoint of this study was efficacy and toxicity and the secondary endpoint was time to progression and overall survival.


A total of 75 cycles were given, for a mean of 2.68 cycles per patient. The response could be evaluated in 20 patients. Two patients (10%) obtained a partial response, and four patients (20%) had stable disease. The median time to progression and overall survival was 2.5 and 7.6 months, respectively.

Grade 3/4 hematological toxicity included neutropenia in six patients (21.4%), anemia in one (3.6%), and thrombocytopenia in one (3.6%). One (3.6%) patient experienced grade 4 neuropathy, and two (7.2%) patients experienced grade 3 diarrhea.


The 5-fluorouracil and paclitaxel combination treatment seems to be effective in patients with advanced pancreatic cancer that did not respond to a gemcitabine-based regimen.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

    Bokemeyer C, Lampe CS, Clemens MR, Hartmann JT, Quietzsch D, Forkmann L, Kollmannsberger C, Kanz L (1997) A phase II trial of paclitaxel and weekly 24 h infusion of 5-fluorouracil/folinic acid in patients with advanced gastric cancer. Anticancer Drugs 8:396–399

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Burris HA (2005) Recent updates on the role of chemotherapy in pancreatic cancer. Semin Oncol 32:1–3

    Article  CAS  Google Scholar 

  3. 3.

    Burris HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, Cripps MC, Portenoy RK, Storniolo AM, Tarassoff P, Nelson R, Dorr FA, Stephens CD, Von Hoff DD (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15:2403–2413

    PubMed  CAS  Google Scholar 

  4. 4.

    Gebbia V, Maiello E, Giuliani F, Borsellino N, Caruso M, Di Maggio G, Ferrau F, Bordonaro R, Verderame F, Tralongo P, Di Cristina L, Agueli R, Russo P, Colucci G (2007) Second-line chemotherapy in advanced pancreatic carcinoma: a multicenter survey of the Gruppo Oncologico Italia Meridionale on the activity and safety of the FOLFOX4 regimen in clinical practice. Ann Oncol 18(Suppl 6):vi124–vi127

    PubMed  Article  Google Scholar 

  5. 5.

    Glimelius B, Hoffman K, Sjödén PO, Jacobsson G, Sellström H, Enander LK, Linné T, Svensson C (1996) Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol 7:593–600

    PubMed  CAS  Google Scholar 

  6. 6.

    Heinemann V, Quietzsch D, Gieseler F, Gonnermann M, Schönekäs H, Rost A, Neuhaus H, Haag C, Clemens M, Heinrich B, Vehling-Kaiser U, Fuchs M, Fleckenstein D, Gesierich W, Uthgenannt D, Einsele H, Holstege A, Hinke A, Schalhorn A, Wilkowski R (2006) Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol 24:3946–3952

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Ignatiadis M, Polyzos A, Stathopoulos GP, Tselepatiotis E, Christophylakis C, Kalbakis K, Vamvakas L, Kotsakis A, Potamianou A, Georgoulias V (2006) A multicenter phase II study of docetaxel in combination with gefitinib in gemcitabine-pretreated patients with advanced/metastatic pancreatic cancer. Oncology 71:159–163

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66

    PubMed  Google Scholar 

  9. 9.

    Kano Y, Akutsu M, Tsunoda S, Ando J, Matsui J, Suzuki K, Ikeda T, Inoue Y, Adachi K (1996) Schedule-dependent interaction between paclitaxel and 5-fluorouracil in human carcinoma cell lines in vitro. Br J Cancer 74:704–710

    PubMed  CAS  Google Scholar 

  10. 10.

    King TC, Estalilla OC, Safran H (1999) Role of p53 and p16 gene alterations in determining response to concurrent paclitaxel and radiation in solid tumor. Semin Radiat Oncol 9:4–11

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Korean national statistical office (2006) Annual report on the cause of death statistics. Korean national statistical office, p 17

  12. 12.

    Kulke MH, Blaszkowsky LS, Ryan DP, Clark JW, Meyerhardt JA, Zhu AX, Enzinger PC, Kwak EL, Muzikansky A, Lawrence C, Fuchs CS (2007) Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer. J Clin Oncol 25:4787–4792

    PubMed  Article  CAS  Google Scholar 

  13. 13.

    Mallinson CN, Rake MO, Cocking JB, Fox CA, Cwynarski MT, Diffey BL, Jackson GA, Hanley J, Wass VJ (1980) Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomised, multicentre trial. Br Med J 281:1589–1591

    PubMed  CAS  Article  Google Scholar 

  14. 14.

    Milella M, Gelibter A, Di Cosimo S, Bria E, Ruggeri EM, Carlini P, Malaguti P, Pellicciotta M, Terzoli E, Cognetti F (2004) Pilot study of celecoxib and infusional 5-fluorouracil as second-line treatment for advanced pancreatic carcinoma. Cancer 101:133–138

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Mitry E, Ducreux M, Ould-Kaci M, Boige V, Seitz JF, Bugat R, Breau JL, Bouché O, Etienne PL, Tigaud JM, Morvan F, Cvitkovic E, Rougier P (2006) Oxaliplatin combined with 5-FU in second line treatment of advanced pancreatic adenocarcinoma. Results of a phase II trial. Gastroenterol Clin Biol 30:357–363

    PubMed  CAS  Article  Google Scholar 

  17. 17.

    Oettle H, Arnold D, Esser M, Huhn D, Riess H (2000) Paclitaxel as weekly second-line therapy in patients with advanced pancreatic carcinoma. Anticancer Drugs 11:635–638

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Palmer KR, Kerr M, Knowles G, Cull A, Carter DC, Leonard RC (1994) Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Br J Surg 81:882–885

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Safran H, Moore T, Iannitti D, Dipetrillo T, Akerman P, Cioffi W, Harrington D, Quirk D, Rathore R, Cruff D, Vakharia J, Vora S, Savarese D, Wanebo H (2001) Paclitaxel and concurrent radiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 49:1275–1279

    PubMed  CAS  Google Scholar 

  20. 20.

    Safran H, Rathore R (2002) Paclitaxel as a radiation sensitizer for locally advanced pancreatic cancer. Crit Rev Oncol Hematol 43:57–62

    PubMed  Article  Google Scholar 

  21. 21.

    Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Tsavaris N, Kosmas C, Skopelitis H, Gouveris P, Kopterides P, Kopteridis P, Loukeris D, Sigala F, Zorbala-Sypsa A, Felekouras E, Papalambros E (2005) Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: A phase II study. Invest New Drugs 23:369–375

    PubMed  Article  CAS  Google Scholar 

  23. 23.

    Ulrich-Pur H, Raderer M, Verena Kornek G, Schüll B, Schmid K, Haider K, Kwasny W, Depisch D, Schneeweiss B, Lang F, Scheithauer W (2003) Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. Br J Cancer 88:1180–1184

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Yeh KH, Lu YS, Hsu CH, Lin JF, Hsu C, Kuo SH, Li SJ, Cheng AL (2005) Phase II study of weekly paclitaxel and 24-hour infusion of high-dose 5-fluorouracil and leucovorin in the treatment of recurrent or metastatic gastric cancer. Oncology 69:88–95

    PubMed  Article  CAS  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Si Young Song.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kim, Y.J., Bang, S., Park, J.Y. et al. Phase II study of 5-fluorouracil and paclitaxel in patients with gemcitabine-refractory pancreatic cancer. Cancer Chemother Pharmacol 63, 529–533 (2009).

Download citation


  • Pancreatic cancer
  • Paclitaxel
  • 5-Fluorouracil
  • Gemcitabine