Skip to main content

Advertisement

SpringerLink
Log in

The efficacy of hybrid chemotherapy with intravenous oxaliplatin and folinic acid and intra-hepatic infusion of 5-fluorouracil in patients with colorectal liver metastases: a phase II study

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

Summary

Intra-arterial chemotherapy in patients with liver metastases from colorectal cancer has some limitations such as hepatic toxicity and extra-hepatic progression.

With the aim of overcoming these limitations, a phase II trial was designed to assess the efficacy and tolerability of a hybrid chemotherapy regimen with systemic infusion of oxaliplatin and folinic acid associated with intra-arterial 5-fluorouracil.

Thirty-nine patients with colorectal liver metastases were recruited. The median age was 59 years, 30 patients (77%) had synchronous metastases, and half of the patients were chemo-naive. A total of 313 chemotherapy cycles were administered (median number 8). Treatment was well tolerated and hepatic toxicity negligible. Out of 34 evaluable patients an ORR of 41%. was observed. Eight patients (21%) underwent radical liver surgery. The median time to progression (TTP) was 10 months (range 2–63) and the median overall survival (OS) 21 months (range 6–63). Extra-hepatic progression was observed in six patients.

Our results suggest that this regimen is active even if technical complications are frequent. Our aim to reduce hepatic toxicity and extra-hepatic progression was reached.

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
Fig. 3

Similar content being viewed by others

References

  1. Skibber JM, Minsky BD, Hoff PM (2001) Cancer of the colon. In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer—principles & practice of oncology, 6th edn. Lippincott Willimas & Wilkins, Philadelphia, pp 1216–1271

    Google Scholar 

  2. de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938–2947

    PubMed  Google Scholar 

  3. 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

    Article  PubMed  CAS  Google Scholar 

  4. Ensminger WD (2002) Intrahepatic arterial infusion of chemotherapy: pharmacologic principles. Semin Oncol 29:119–125

    Article  PubMed  CAS  Google Scholar 

  5. Chan R, Kerr D (2004) Hepatic arterial chemotherapy for colorectal cancer liver metastases: a review of advances in 2003. Curr Opin Oncol 16:378–384

    Article  PubMed  Google Scholar 

  6. Lorenz M, Müller H-H (2000) For the German Cooperative Group on the liver metastases: randomized, multicenter trial of fluoruracil plus leucovorin administered either via hepatic arterial or intravenous infusion versus fluorodeoxyuridine administered via hepatic arterial infusion in patients with nonresectable liver metastases from colorectal carcinoma. J Clin Oncol 18:243–254

    PubMed  CAS  Google Scholar 

  7. Kerr DJ, McArdle CS, Ledermann J, Taylor I, Sherlock DJ, Schlag PM, Buckels J, Mayer D, Cain D, Stephens RJ (2003) Intrahepatic arterial versus intravenous fluorouracil and folinic acid for colorectal cancer liver metastases: a multicentre randomised trial. Lancet 361:368–373

    Article  PubMed  CAS  Google Scholar 

  8. Cohen AD, Kemeny NE (2003) An update on hepatic arterial infusion chemotherapy for colorectal cancer. The Oncologist 8:553–566

    Article  PubMed  Google Scholar 

  9. Chamberlain RS (2004) Laparoscopic placement of hepatic arterial pumps: a true advance or a lot effort for a procedure with diminishing role? Ann Surg Oncol 11:558–559

    Article  PubMed  Google Scholar 

  10. Urbach DR, Herron DM, Khajanchee YS, Swanstrom LL, Hansen PD (2001) Laparoscopic hepatic artery infusion pump placement. Arch Surg 136:700–704

    Article  PubMed  CAS  Google Scholar 

  11. Oberfield RA, Sampson E, Heatley J (2004) Hepatic artery infusion chemotherapy for metastatic colorectal cancer to the liver at the Lahey Clinic: comparison between two methods of treatment, surgical versus percutaneous catheter placement. Am J Clin Oncol 27:376–383

    Article  PubMed  Google Scholar 

  12. Kemeny N, Gonen M, Sullivan D, Schwartz L, Benedetti F, Saltz L, Stockman J, Fong Y, Jarnagin W, Bertino J, Tong W, Paty P (2001) Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. J Clin Oncol 19:2687–2695

    PubMed  CAS  Google Scholar 

  13. Kemeny N, Jarnagin W, Gonen M, Stockman J, Blumgart L, Sperber D, Hummer A, Fong Y (2003) Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer. J Clin Oncol 21:3303–3309

    Article  PubMed  CAS  Google Scholar 

  14. Kern W, Beckert B, Lang N, Waggershauser T, Braess J, Schalhorn A, Hiddemann W (2000) Hepatic arterial infusion with oxaliplatin, folinic acid, and 5-fluorouracil in patients with hepatic metastases from colorectal, cancer: role of carcino-embryonic antigen in assessment of response. Anticancer Res 20:4973–4976

    PubMed  CAS  Google Scholar 

  15. Kemeny N, Jarnagin W, Paty P, Gonen M, Schwartz L, Morse M, Leonard G, D’Angelica M, DeMatteo R, Blumgart L, Fong Y (2005) Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol 23:4888–4896

    Article  PubMed  CAS  Google Scholar 

  16. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Controlled Clin Trials 10:1–10

    Article  PubMed  CAS  Google Scholar 

  17. Liu LX, Zhang WH, Jiang HC (2003) Current treatment for liver metastases from colorectal cancer. World J Gastroenterol 9:193–200

    PubMed  Google Scholar 

  18. Haller DG (2000) Waiting for the definitive trial of hepatic arterial chemotherapy from colorectal cancer. J Clin Oncol 18:239–242

    PubMed  CAS  Google Scholar 

  19. Ducreux M, Ychou M, Laplanche A, Gamelin E, Lasser P, Husseini F, Quenet F, Viret F, Jacob JH, Boige V, Elias D, Delperro JR, Luboinski M (2005) Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: a trial of the Gastrointestinal Group of the Fédération Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol 23:4881–4887

    Article  PubMed  CAS  Google Scholar 

  20. Dizon DS, Kemeny NE (2002) Intrahepatic arterial infusion of chemotherapy: clinical results. Semin Oncol 29:126–135

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Via Manzoni 56, 20089, Rozzano (Milano), Italy

    Carlo Carnaghi, Armando Santoro, Lorenza Rimassa, Giuseppe Gullo, Monica Zuradelli, Giovanni Abbadessa, Ilaria Marcon & Isabella Garassino

  2. Surgical Oncology Unit, Istituto Clinico Humanitas, Via Manzoni 56, 20089, Rozzano (Milano), Italy

    Roberto Doci

  3. General and Mini-Invasive Surgery Unit, Istituto Clinico Humanitas, Via Manzoni 56, 20089, Rozzano (Milano), Italy

    Riccardo Rosati

  4. Radiology Unit, Istituto Clinico Humanitas, Via Manzoni 56, 20089, Rozzano (Milano), Italy

    Vittorio Pedicini

  5. Clinical Trials Office, Istituto Clinico Humanitas, Via Manzoni 56, 20089, Rozzano (Milano), Italy

    Emanuela Morenghi

  6. Istituto Clinico Humanitas, Via Manzoni 56, 20089, Rozzano (Milano), Italy

    Carlo Carnaghi

Authors
  1. Carlo Carnaghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Armando Santoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lorenza Rimassa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Roberto Doci
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Riccardo Rosati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vittorio Pedicini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giuseppe Gullo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Monica Zuradelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Giovanni Abbadessa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Emanuela Morenghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Ilaria Marcon
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Isabella Garassino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlo Carnaghi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carnaghi, C., Santoro, A., Rimassa, L. et al. The efficacy of hybrid chemotherapy with intravenous oxaliplatin and folinic acid and intra-hepatic infusion of 5-fluorouracil in patients with colorectal liver metastases: a phase II study. Invest New Drugs 25, 479–485 (2007). https://doi.org/10.1007/s10637-007-9048-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10637-007-9048-5

Keywords

Search

Navigation