Skip to main content

Advertisement

Log in

Pilot study of irinotecan/oxalipltin (IROX) combination chemotherapy for patients with gemcitabine- and 5-fluorouracil- refractory pancreatic cancer

  • PHASE II STUDIES
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

Background Gemcitabine- and 5-fluorouracil (5-FU)- based chemotherapy is a commonly used adjuvant or palliative treatment for patients with pancreatic cancer. However, a standard chemotherapy regimen has yet to be developed for patients refractory to gemcitabine and 5-FU treatment. We attempted to evaluate the efficacy and safety of a combination of irinotecan and oxaliplatin (IROX) as a salvage treatment for patients with gemcitabine- and 5-FU- refractory pancreatic cancer. Patients and Methods Patients with advanced pancreatic cancer who were refractory to prior gemcitabine- and 5-FU- based chemotherapy were enrolled in this study. IROX chemotherapy was administered as follows: Irinotecan, 150 mg/m2 on day 1; and oxaliplatin, 85 mg/m2 on day 1 over 90 min every 2 weeks. Result From Mar. 2006 to Dec. 2008, a total of 14 patients were administered 50 cycles of chemotherapy. The male-to-female ratio of the patient group was 11:3. These patients ranged in age from 48 to 73 years (median 65.5 years old). 3 patients (21.4%) evidenced partial responses. four patients (28.6%) exhibited stable disease. The median time to progression and overall survival time were 1.4 (95% CI: 1.2–1.6) months and 4.1 (95% CI: 2.0–6.2) months, respectively. Major hematologic toxicities included grade 1–2 anemia (88%), neutropenia (36%), thrombocytopenia (30%), and grade 3–4 neutropenia (10%). The most frequently detected non-hematological toxicities were grade 3 diarrheas (14%). Conclusion The IROX regimen appears to constitute a feasible and tolerable salvage therapy in patients with advanced pancreatic cancer who have been previously treated with gemcitabine- and 5-FU-based chemotherapy.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Burris HA III, 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

    CAS  PubMed  Google Scholar 

  2. Herrmann R, Bodoky G, Ruhstaller T, Glimelius B, Bajetta E, Schuller J, Saletti P, Bauer J, Figer A, Pestalozzi B, Kohne CH, Mingrone W, Stemmer SM, Tamas K, Kornek GV, Koeberle D, Cina S, Bernhard J, Dietrich D, Scheithauer W (2007) Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol 25:2212–2217. doi:10.1200/JCO.2006.09.0886

    Article  CAS  PubMed  Google Scholar 

  3. Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W (2007) 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 25:1960–1966. doi:10.1200/JCO.2006.07.9525

    Article  CAS  PubMed  Google Scholar 

  4. Ducreux M, Boige V, Malka D (2007) Treatment of advanced pancreatic cancer. Semin Oncol 34:S25–S30. doi:10.1053/j.seminoncol.2007.01.006

    Article  CAS  PubMed  Google Scholar 

  5. Heinemann V, Boeck S, Hinke A, Labianca R, Louvet C (2008) Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer 8:82. doi:10.1186/1471-2407-8-82

    Article  PubMed  Google Scholar 

  6. Evans DB, Lee JE, Pisters PW, Charnsangavej C, Ellis LM, Chiao PJ, Lenzi R, Abbruzzese JL (1997) Advances in the diagnosis and treatment of adenocarcinoma of the pancreas. Cancer Treat Res 90:109–125

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  8. Creemers GJ, Lund B, Verweij J (1994) Topoisomerase I inhibitors: topotecan and irenotecan. Cancer Treat Rev 20:73–96. doi:10.1016/0305-7372(94)90011-6

    Article  CAS  PubMed  Google Scholar 

  9. Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355:1041–1047. doi:10.1016/S0140-6736(00)02034-1

    Article  CAS  PubMed  Google Scholar 

  10. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL (2000) Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 343:905–914. doi:10.1056/NEJM200009283431302

    Article  CAS  PubMed  Google Scholar 

  11. Bissery MC, Vrignaud P, Lavelle F, Chabot GG (1996) Experimental antitumor activity and pharmacokinetics of the camptothecin analog irinotecan (CPT-11) in mice. Anticancer Drugs 7:437–460. doi:10.1097/00001813-199606000-00010

    Article  CAS  PubMed  Google Scholar 

  12. Wagener DJ, Verdonk HE, Dirix LY, Catimel G, Siegenthaler P, Buitenhuis M, Mathieu-Boue A, Verweij J (1995) Phase II trial of CPT-11 in patients with advanced pancreatic cancer, an EORTC early clinical trials group study. Ann Oncol 6:129–132

    CAS  PubMed  Google Scholar 

  13. Kornmann M, Fakler H, Butzer U, Beger HG, Link KH (2000) Oxaliplatin exerts potent in vitro cytotoxicity in colorectal and pancreatic cancer cell lines and liver metastases. Anticancer Res 20:3259–3264

    CAS  PubMed  Google Scholar 

  14. Monti P, Marchesi F, Reni M, Mercalli A, Sordi V, Zerbi A, Balzano G, Di Carlo V, Allavena P, Piemonti L (2004) A comprehensive in vitro characterization of pancreatic ductal carcinoma cell line biological behavior and its correlation with the structural and genetic profile. Virchows Arch 445:236–247. doi:10.1007/s00428-004-1053-x

    Article  CAS  PubMed  Google Scholar 

  15. Raymond E, Faivre S, Woynarowski JM, Chaney SG (1998) Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 25:4–12

    CAS  PubMed  Google Scholar 

  16. 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 10.1093/jnci/92.3.205

    Article  CAS  PubMed  Google Scholar 

  17. Neoptolemos JP, Stocken DD, Tudur Smith C, Bassi C, Ghaneh P, Owen E, Moore M, Padbury R, Doi R, Smith D, Buchler MW (2009) Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: composite data from the ESPAC-1 and -3(v1) trials. Br J Cancer 100:246–250. doi:10.1038/sj.bjc.6604838

    Article  CAS  PubMed  Google Scholar 

  18. Kim HM, Bang S, Park JY, Seong J, Song SY, Chung JB, Park SW (2009) Phase II trial of S-1 and concurrent radiotherapy in patients with locally advanced pancreatic cancer. Cancer Chemother Pharmacol 63:535–541. doi:10.1007/s00280-008-0836-1

    Article  CAS  PubMed  Google Scholar 

  19. Lee S, Oh SY, Kim BG, Kwon HC, Kim SH, Rho MH, Kim YH, Rho MS, Jeong JS, Kim HJ (2009) Second-Line Treatment With a Combination of Continuous 5-Fluorouracil, Doxorubicin, and Mitomycin-C (Conti-Fam) in Gemcitabine-Pretreated Pancreatic and Biliary Tract Cancer. Am J Clin Oncol

  20. Kim YJ, Bang S, Park JY, Park SW, Chung JB, Song SY (2009) Phase II study of 5-fluorouracil and paclitaxel in patients with gemcitabine-refractory pancreatic cancer. Cancer Chemother Pharmacol 63:529–533. doi:10.1007/s00280-008-0822-7

    Article  CAS  PubMed  Google Scholar 

  21. Tsavaris N, Kosmas C, Skopelitis H, Gouveris P, Kopterides 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. doi:10.1007/s10637-005-1446-y

    Article  CAS  PubMed  Google Scholar 

  22. Cantore M, Rabbi C, Fiorentini G, Oliani C, Zamagni D, Iacono C, Mambrini A, Del Freo A, Manni A (2004) Combined irinotecan and oxaliplatin in patients with advanced pre-treated pancreatic cancer. Oncology 67:93–97. doi:10.1159/000080993

    Article  CAS  PubMed  Google Scholar 

  23. Ulrich-Pur H, Raderer M, Verena Kornek G, Schull 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. doi:10.1038/sj.bjc.6600883

    Article  CAS  PubMed  Google Scholar 

  24. Reni M, Pasetto L, Aprile G, Cordio S, Bonetto E, Dell’Oro S, Passoni P, Piemonti L, Fugazza C, Luppi G, Milandri C, Nicoletti R, Zerbi A, Balzano G, Di Carlo V, Brandes AA (2006) Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer. Br J Cancer 94:785–791. doi:10.1038/sj.bjc.6603026

    Article  CAS  PubMed  Google Scholar 

  25. 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. doi:10.1159/000106064

    Article  CAS  PubMed  Google Scholar 

  26. Yi SY, Park YS, Kim HS, Jun HJ, Kim KH, Chang MH, Park MJ, Uhm JE, Lee J, Park SH, Park JO, Lee JK, Lee KT, Lim HY, Kang WK (2009) Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer. Cancer Chemother Pharmacol 63:1141–1145. doi:10.1007/s00280-008-0839-y

    Article  CAS  PubMed  Google Scholar 

  27. Burris HA III, Rivkin S, Reynolds R, Harris J, Wax A, Gerstein H, Mettinger KL, Staddon A (2005) Phase II trial of oral rubitecan in previously treated pancreatic cancer patients. Oncologist 10:183–190. doi:10.1634/theoncologist.10-3-183

    Article  CAS  PubMed  Google Scholar 

  28. Oettle H, Pelzer U, Stieler J, Hilbig A, Roll L, Schwaner I, Adler M, Detken S, Dörken B, Riess H (2005) Oxaliplatin/folic acid/5-fluorouracil [24 h] (OFF) plus best supportive care versus best supportive care alone (BSC) in second-line therapy of gemcitabine refractory advanced pancreatic cancer (CONKO 003). J Clin Oncol 23:201s, abstract 4031

    Google Scholar 

  29. Ashley AC, Sargent DJ, Alberts SR, Grothey A, Campbell ME, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK, Findlay BP, Pitot HC, Goldberg RM (2007) Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) : intergroup trial N9741 in first-line treatment of metastatic colorectal cancer. Cancer 110:670–677. doi:10.1002/cncr.22831

    Article  CAS  PubMed  Google Scholar 

  30. Chang MH, Kim KH, Jun HJ, Kim HS, Yi SY, Uhm JE, Park MJ, Lim DH, Ji SH, Hwang IG, Lee J, Park YH, Ahn JS, Ahn MJ, Park K (2009) Irinotecan and oxaliplatin combination as the first-line treatment for patients with advanced non-small cell lung cancer Cancer Chemother Pharmacol [Epub ahead of print]

Download references

Acknowledgement

This paper was supported by the Dong-A University Research Fund.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jung Hun Kang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oh, S.Y., Kim, H.J., Kim, T.H. et al. Pilot study of irinotecan/oxalipltin (IROX) combination chemotherapy for patients with gemcitabine- and 5-fluorouracil- refractory pancreatic cancer. Invest New Drugs 28, 343–349 (2010). https://doi.org/10.1007/s10637-009-9265-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-009-9265-1

Keywords

Navigation