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Sequential FOLFOX-6 and gemcitabine for locally advanced and/or metastatic pancreatic cancer

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Abstract

This prospective phase II trial aims to evaluate the sequential FOLFOX-6 and gemcitabine followed by adapted maintenance for advanced pancreatic cancer. Treatment included FOLFOX-6 for 4 cycles, followed sequentially by gemcitabine for 3 cycles. Patients, who show clinical benefit after both sequences, will receive maintenance treatment based on the investigator’s discretion. From January 2005 to June 2008, 32 patients with median age of 63 were included; 75% of patients had metastatic disease, 81% had pure adenocarcinoma, while 19% had adenocarcinoma with a neuroendocrine component. There were 22% PR and 22% SD resulting in 44% tumor growth control. Under FOLFOX, grade 3/4 toxicities were neutropenia in 8 patients, thrombocytopenia and anemia in 3 patients each, and diarrhea in 2 patients. Under Gem, grade 3/4 neutropenia was observed in 4 patients, thrombocytopenia and anemia were observed in 2 patients, and hand-foot syndrome was observed in 3 patients. The median TTP and OS were 4 and 10 months, respectively. In APC, FOLFOX-6 regimen followed by gemcitabine achieved an interesting RR within a tolerable level of toxicity. This regimen seems to warrant further investigation to confirm its efficacy.

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References

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  2. Surveillance Epidemiology and End Results (SEER). U.S. Cancer Statistics: 1999–2007 Incidence and mortality report. 2010. http://www.seer.cancer.gov/publications/uscs.html.

  3. Cullinan SA, Moertel C, Wieand HS, et al. A phase III trial on the therapy of advanced pancreatic carcinoma. Evaluations of the Mallinson regimen and combined 5-fluorouracil, doxorubicin and cisplatin. Cancer. 1990;65:2207–12.

    Article  PubMed  CAS  Google Scholar 

  4. Bertheault-Cvitkovic F, Lévi F, Soussan S, et al. Circadian rhythm modulated chemotherapy 5-fluorouracil: a pilot study in patients with pancreatic adenocarcinoma. Eur J Cancer. 1993;29A:1851–4.

    Article  PubMed  CAS  Google Scholar 

  5. Tajiri H, Yoshimori M, Okazaki N, et al. Phase II study of continuous venous infusion of 5-fluorouracil in advanced pancreatic cancer. Oncology. 1991;48:18–21.

    Article  PubMed  CAS  Google Scholar 

  6. Ducreux M, Rougier P, Pignon JP, et al. A randomised trial comparing 5-FU with 5-FU plus Cisplatin in advanced pancreatic carcinoma. Ann Oncol. 2002;13:1185–91.

    Article  PubMed  CAS  Google Scholar 

  7. Burris HA 3rd, 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(6):2403–13.

    PubMed  CAS  Google Scholar 

  8. Berlin JD, Catalano P, Thomas JP, et al. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol. 2002;20(15):3270–5.

    Article  PubMed  CAS  Google Scholar 

  9. Heinemann V, Labianca R, Hinke A, Louvet C, et al. Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study. Ann Oncol. 2007;18(10):1652–9.

    Article  PubMed  CAS  Google Scholar 

  10. Lévi F, Zidani R, Misset JL. Randomised multicenter trial of chronotherapy with oxaliplatin, fluorouracil and folinic acid in metastatic colorectal cancer. International Organization for Cancer Chronotherapy. Lancet. 1997;350:681–6.

    Google Scholar 

  11. De Gramont A, Figer A, Seymour M, et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18(16):2938–47.

    PubMed  Google Scholar 

  12. Kormann M, Kakler H, Butzer U, et al. Oxaliplatin exerts potent in vitro cytotoxicity in colorectal and pancreatic cancer cell lines and liver metastases. Anticancer Res. 2000;20:3259–64.

    Google Scholar 

  13. Raymond E, Lawrence R, Izbicka E, et al. Activity of oxaliplatin against human tumor colony-forming units. Clin Cancer Res. 1998;4(4):1021–9.

    PubMed  CAS  Google Scholar 

  14. Raymond E, Faivre S, Woynarowski JM, et al. Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol. 1998;25(Suppl 5):4–12.

    PubMed  CAS  Google Scholar 

  15. Cersosimo RJ. Oxaliplatin-associated neuropathy: a review. Ann Pharmacother. 2005;39(1):128–35.

    PubMed  CAS  Google Scholar 

  16. Maindrault-Goebel F, Louvet C, André T, et al. Oxaliplatin added to the simplified bimonthly leucovorin and 5-FU regimen as second-line therapy for metastatic colorectal cancer (FOLFOX 6). Eur J Cancer. 1999;9:1338–42.

    Article  Google Scholar 

  17. Culy CR, Clemett D, Wiseman LR. Oxaliplatin. A review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies. Drugs. 2000;60(4):895–924.

    Article  PubMed  CAS  Google Scholar 

  18. Ducreux M, Mitry E, Ould-Kaci M, et al. Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients. Ann Oncol. 2004;15:467–73.

    Article  PubMed  CAS  Google Scholar 

  19. Louvet C, Labianca R, Hammel P, et al. 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. 2005;20(23):3509–16.

    Article  Google Scholar 

  20. Louvet C, Andre T, Liedo G, et al. Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol. 2002;20(6):1512–8.

    Article  PubMed  CAS  Google Scholar 

  21. Ghosn M, Farhat F, Kattan J, et al. FOLFOX-6 combination as the first-line treatment of locally advanced and/or metastatic pancreatic cancer. Am J Clin Oncol. 2007;30(1):15–20.

    Article  PubMed  CAS  Google Scholar 

  22. Stathopoulos G, Syrigos K, Aravantinos G, et al. A multicenter phase III trial comparing irinotecan-gemcitabine (IG) with gemcitabine (G) monotherapy as first-line treatment in patients with locally advanced or metastatic pancreatic cancer. Br J Cancer. 2006;95(5):587–92.

    Article  PubMed  CAS  Google Scholar 

  23. Heinemann V, Hoehler T, Seipelt G, et al. Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer. Ann Oncol. 2008;19(2):340–7.

    Article  PubMed  Google Scholar 

  24. Song K, Do Y, Chang H, et al. A phase II study of capecitabine plus gemcitabine in patients with locally advanced or metastatic pancreatic cancer. Cancer Chemother Pharmacol. 2008;62(5):763–8.

    Article  PubMed  CAS  Google Scholar 

  25. Moore M, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(15):1960–6.

    Article  PubMed  CAS  Google Scholar 

  26. Kindler HL, et al. Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the cancer and leukemia group B (CALGB 80303). J Clin Oncol. 2010;28(22):3617–22.

    Article  PubMed  CAS  Google Scholar 

  27. Philip PA. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced pancreatic adenocarcinoma: southwest oncology group–directed intergroup trial S0205. J Clin Oncol. 2010;28(22):3605–10.

    Article  PubMed  CAS  Google Scholar 

  28. Colucci G, et al. Randomized phase III trial of gemcitabine plus cisplatin compared with single-agent gemcitabine as first-line treatment of patients with advanced pancreatic cancer: the GIP-1 study. J Clin Oncol. 2010;28:1645–51.

    Article  PubMed  CAS  Google Scholar 

  29. Popli E, Feng Y, Berlin J, et al. Phase III, randomized study of gemcitabine and oxaliplatin versus gemcitabine (fixed-dose rate infusion) compared with gemcitabine (30-minute infusion) in patients with pancreatic carcinoma E6201: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009;27(23):3778–85.

    Article  Google Scholar 

  30. Bernhard J, et al. Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial. J Clin Oncol. 2008;26(22):3695–701.

    Article  PubMed  CAS  Google Scholar 

  31. Conroy T, Desseigne F, Ychou M, et al. Folforinox versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.

    Article  PubMed  CAS  Google Scholar 

  32. Oberstein PE, Saif M. First-line treatment for advanced pancreatic cancer. S from the “2011 ASCO gastrointestinal cancers symposium”. J Pancreas (Online). 2011;12(2):96–100.

    Google Scholar 

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Acknowledgments

This study was partially supported by an unrestricted grant from sanofi-aventis.

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Correspondence to M. Ghosn.

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This study was conducted for the Cancer Research Group/Collaborative Group, Beirut, Lebanon.

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Ghosn, M., Saroufim, A., Kattan, J. et al. Sequential FOLFOX-6 and gemcitabine for locally advanced and/or metastatic pancreatic cancer. Med Oncol 29, 2831–2837 (2012). https://doi.org/10.1007/s12032-012-0197-9

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  • DOI: https://doi.org/10.1007/s12032-012-0197-9

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