Journal of Gastrointestinal Cancer

, Volume 44, Issue 3, pp 313–317 | Cite as

Oxaliplatin Plus 5-Fluorouracil and Folinic Acid (OFF) in Gemcitabine-Pretreated Advanced Pancreatic Cancer: A Phase II Study

Original Research

Abstract

Background

Despite median survival of less than 6 months, there is a significant proportion of advanced pancreatic cancer patients who progress on gemcitabine that remains fit, and these patients are candidates for second-line treatment.

Objective

The objective of this study is to evaluate the efficacy and safety of oxaliplatin plus 5-fluorouracil and folinic acid in patients with gemcitabine-pretreated advanced pancreatic cancer.

Patients and Methods

Thirty patients with advanced pancreatic cancer who were pretreated with gemcitabine received oxaliplatin (85 mg/m2) on days 1 and 15 followed by leucovorin (20 mg/m2) and 5-fluorouracil (500 mg/m2) on days 1, 8, and 15. The cycle was repeated every 3 weeks.

Results

The majority of patients (80 %) had locally advanced disease. Median age was 63 years, and 60 % were males. The liver was the most common site of metastasis. Partial response was observed in 2 patients (6.7 %) and stable disease in 6 patients (20 %), while 12 patients progressed (40 %). Improved performance status was reported in 10 patients (33.3 %). The median duration of response was 13 weeks, and median overall survival was 22 weeks. There was no grade 4 toxicity apart from grade 4 neutropenia in 6.6 % of patients. Neutropenia (46.5 %) and neuropathy (43.2 %) were the most common toxicities, while hand–foot syndrome was the least frequent one (20 %). There were no treatment-related deaths. The 6-month survival rate was 30 %.

Conclusion

This regimen is feasible and active with an acceptable toxicity; however, further investigation in phase III trial is needed.

Keywords

Oxaliplatin Locally advanced pancreatic cancer Pretreated pancreatic cancer Oxaliplatin plus 5-fluorouracil and folinic acid 

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    National Cancer Institute. Surveillance Epidemiology and End Results (SEER) Stat Fact Sheets. 2009. http://seer.cancer.gov/csr/1975_2009_pops09, based on November 2011 SEER data submission, posted to the SEER web site, April 2012.
  2. 2.
    Ferlay J, Autier P, Boniol M, Heanue M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007;18:581–92.PubMedCrossRefGoogle Scholar
  3. 3.
    Burris 3rd HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.PubMedGoogle Scholar
  4. 4.
    Androulakis N, Syrigosk, Polyzos A, Hellenic Oncology Research Group, et al. Oxaliplatin for pretreated patients with advanced or metastatic pancreatic cancer: a multicenter phase II study. Cancer Invest. 2005;93:9–12.CrossRefGoogle Scholar
  5. 5.
    Hochster H, Chachoua A, Speyer J, et al. Oxaliplatin with weekly bolus fluorouracil and low-dose leucovorin as first-line therapy for patients with colorectal cancer. J Clin Oncol. 2003;21(14):2703–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Guarneri D, Venturino A, Addamo G. Weekly oxaliplatin, bolus 5-FU and LV as first line treatment of metastatic colorectal cancer: preliminary results. Ann Oncol. 2002;13 Suppl 5:87.Google Scholar
  7. 7.
    Ravaioli A, Marangolo M, Pasqiuni E, et al. Bolus fluorouracil and leucovorin with oxaliplatin as first line treatment in metastatic colorectal cancer. J Clin Oncol. 2002;20(10):2545–50.PubMedCrossRefGoogle Scholar
  8. 8.
    Eisenhaurer EA, Therasse P, Borgaerts J, et al. New response evaluation criteria in solid tumors: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefGoogle Scholar
  9. 9.
    Trotti A, Colevas AD, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol. 2003;13:176–81.PubMedCrossRefGoogle Scholar
  10. 10.
    Carrato A, Gallego J, Diaz-Rubio E. Oxaliplatin: results in colorectal carcinoma. Crit Rev Oncol Hematol. 2002;44(1):29–44.PubMedCrossRefGoogle Scholar
  11. 11.
    Cheeseman SL, Joel SP, Chester JD, et al. A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer. 2002;87(4):393–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Goldberg RM, Morton RF, Sargent DJ, et al. N9741: oxaliplatin or CPT-11 +5FU/LV or oxaliplatin + CPT-11 in advanced colorectal cancer. Paper presented at the 39th annual meeting of the American Society of Clinical Oncology, Chicago; 2003. 31 May–3 June 2003.Google Scholar
  13. 13.
    Tsavaris N, Kosmas C, Skopelitis H, et al. Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: a phase II study. Invest New Drugs. 2005;23:369–75.PubMedCrossRefGoogle Scholar
  14. 14.
    Schrag D, Archer L, Wang X, et al. A patterns-of-care study of post-progression treatment among patients with advanced pancreas cancer after gemcitabine therapy on Cancer and Leukemia Group B (CALGB) study #80303. ASCO Annual Meeting Proceedings. J Clin Oncol. 2007;25(Suppl pt 1):4524.Google Scholar
  15. 15.
    Pelzer U, Kubica K, Stieler J, et al. A randomized trial in patients with gemcitabine refractory pancreatic cancer. Final results of the CONKO 003 study. J Clin Oncol. 2008;26:A4058.CrossRefGoogle Scholar
  16. 16.
    Altwegg R, Ychou M, Guillaumon V, et al. Second-line therapy for gemcitabine-pretreated advanced or metastatic pancreatic cancer. World J Gastroenterol. 2012;18(12):1357–64.PubMedCrossRefGoogle Scholar
  17. 17.
    Cantore M, Rabbi C, Fiorentini G, et al. Combined irinotecan and oxaliplatin in patients with advanced pre-treated pancreatic cancer. Oncology. 2004;67:93–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Van Laethem JL, Polus M, Marechal R, et al. Gemcitabine and oxaliplatin in gemcitabine-refractory advanced pancreatic cancer: a phase II study. Proc Am Soc Clin Oncol. 2004;23:4119.Google Scholar
  19. 19.
    Reni M, Panucci MG, Passoni P, et al. Salvage chemotherapy with mitomycin, docetaxel and irinotecan in metastatic pancreatic adenocarcinoma: a phase I and II trial. Cancer Invest. 2004;22:688–96.PubMedCrossRefGoogle Scholar
  20. 20.
    Milella M, Gelibter A, Di Cosimo S, et al. Pilot study of celecoxib and infusional 5-fluorouracil as second-line treatment for advanced pancreatic cancer. Cancer. 2004;101:133–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Pelzer U, Stieler J, Roll L, et al. Second-line therapy in refractory pancreatic cancer. Results of a phase II study. Onkologie. 2009;32:99–102.PubMedCrossRefGoogle Scholar
  22. 22.
    Boeck S, Heinemann V. The role of second-line chemotherapy for gemcitabine failure in patients with advanced pancreatic cancer. Future Oncol. 2008;4:41–50.PubMedCrossRefGoogle Scholar
  23. 23.
    Morton JP, Lewis BC. Shh signaling and pancreatic cancer: implications for therapy? Cell Cycle. 2007;6:1553–7.PubMedCrossRefGoogle Scholar
  24. 24.
    Mysliviec P, Boucher MJ. Targeting Notch signaling in pancreatic cancer patients—rationale for new therapy. Adv Med Sci. 2009;54:136–42.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Clinical Oncology and Nuclear Medicine, Faculty of MedicineMansoura UniversityMansouraEgypt

Personalised recommendations