Skip to main content

Advertisement

SpringerLink
Log in

Hepatic Intra-Arterial Injection of Drug-Eluting Bead, Irinotecan (DEBIRI) in Unresectable Colorectal Liver Metastases Refractory to Systemic Chemotherapy: Results of Multi-Institutional Study

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Introduction

Response rates and overall outcome for patients who have failed first-line and in some cases second-line chemotherapy are as low as 12% and 7 months, respectively. The aim of this study is to evaluate the efficacy of hepatic arterial sulfonate hydrogel microsphere (drug-eluting beads), irinotecan preloaded therapy (DEBIRI) in metastatic colorectal cancer refractory to systemic chemotherapy.

Methods

This was a multicenter multinational single-arm study of metastatic colorectal cancer patients who received DEBIRI after failing systemic chemotherapy from 10/2006 to 8/2008. Primary endpoints were safety, tolerance, tumor response rates, and overall survival.

Results

Fifty-five patients who had received prior systemic chemotherapy and who underwent a total of 99 DEBIRI treatments were reviewed. The median number of DEBIRI treatments was 2 (range 1–5), median treatment dose was 100 mg (range 100–200 mg), with total hepatic treatment of 200 mg (range 200–650 mg), with 86% of treatments performed as lobar infusion and 30% of patients treated with concurrent simultaneous chemotherapy. Adverse events occurred in 28% of patients with median grade of 2 (range 1–3) with no deaths at 30 days post procedure. Response rates were 66% at 6 months and 75% at 12 months. Overall survival in these patients was 19 months, with progression-free survival of 11 months.

Conclusions

Hepatic arterial drug-eluting bead, irinotecan (DEBIRI) was safe and effective in treatment of metastatic colorectal cancer (MCC) refractory to multiple lines of systemic chemotherapy. DEBIRI is an acceptable therapy for treatment of metastatic colorectal cancer to the liver.

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

Similar content being viewed by others

References

  1. Chen HX, Mooney M, Boron M, et al. Phase II multicenter trial of bevacizumab plus fluorouracil and leucovorin in patients with advanced refractory colorectal cancer: an NCI Treatment Referral Center Trial TRC-0301. J Clin Oncol. 2006;24:3354–60.

    Article  CAS  PubMed  Google Scholar 

  2. Saltz LB, Lenz HJ, Kindler HL, et al. Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. J Clin Oncol. 2007;25:4557–61.

    Article  CAS  PubMed  Google Scholar 

  3. Allen-Mersh TG, Earlam S, Fordy C, et al. Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases. Lancet. 1994;344:1255–60.

    Article  CAS  PubMed  Google Scholar 

  4. Hohn DC, Stagg RJ, Friedman MA, et al. A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial. J Clin Oncol. 1989;7:1646–54.

    CAS  PubMed  Google Scholar 

  5. Kennedy A, Nag S, Salem R, et al. Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol Phys. 2007;68:13–23.

    Article  PubMed  Google Scholar 

  6. Sharma RA, Van Hazel GA, Morgan B, et al. Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy. J Clin Oncol. 2007;25:1099–106.

    Article  CAS  PubMed  Google Scholar 

  7. Martin RC, Edwards MJ, McMasters KM. Morbidity of adjuvant hepatic arterial infusion pump chemotherapy in the management of colorectal cancer metastatic to the liver. Am J Surg. 2004;188:714–21.

    Article  PubMed  Google Scholar 

  8. Martin RC, Joshi J, Robbins K, et al. Transarterial chemoembolization of metastatic colorectal carcinoma with drug-eluting beads, irinotecan (DEBIRI): multi-institutional registry. J Oncol. 2009;2009:539–795.

  9. Martin RC, Robbins K, Tomalty D, et al. Transarterial chemoembolisation (TACE) using irinotecan-loaded beads for the treatment of unresectable metastases to the liver in patients with colorectal cancer: an interim report. World J Surg Oncol. 2009;7:80.

    Article  PubMed  Google Scholar 

  10. Levine MN, Julian JA. Registries that show efficacy: good, but not good enough. J Clin Oncol. 2008;26:5316–9.

    Article  PubMed  Google Scholar 

  11. Choi H, Charnsangavej C, Faria SC, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol. 2007;25:1753–9.

    Article  PubMed  Google Scholar 

  12. Llovet JM, Di Bisceglie AM, Bruix J, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100:698–711.

    Article  PubMed  Google Scholar 

  13. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  14. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–45.

    Article  CAS  PubMed  Google Scholar 

  15. Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2004;22:23–30.

    Article  CAS  PubMed  Google Scholar 

  16. Kohne CH, Van Cutsem E, Wils J, et al. Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986. J Clin Oncol. 2005;23:4856–65.

    Article  PubMed  Google Scholar 

  17. Colucci G, Gebbia V, Paoletti G, et al. Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell’Italia Meridionale. J Clin Oncol. 2005;23:4866–75.

    Article  CAS  PubMed  Google Scholar 

  18. Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–37.

    Article  CAS  PubMed  Google Scholar 

  19. de Gramont A, Vignoud J, Tournigand C, et al. Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer. Eur J Cancer. 1997;33:214–9.

    Article  PubMed  Google Scholar 

  20. Rothenberg ML, Oza AM, Bigelow RH, et al. Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial. J Clin Oncol. 2003;21:2059–69.

    Article  CAS  PubMed  Google Scholar 

  21. Ulrich-Pur H, Kornek GV, Fiebiger W, et al. Multicenter phase II trial of dose-fractionated irinotecan in patients with advanced colorectal cancer failing oxaliplatin-based first-line combination chemotherapy. Ann Oncol. 2001;12:1269–72.

    Article  CAS  PubMed  Google Scholar 

  22. Park SH, Sung JY, Han SH, et al. Oxaliplatin, folinic acid and 5-fluorouracil (FOLFOX-4) combination chemotherapy as second-line treatment in advanced colorectal cancer patients with irinotecan failure: a Korean single-center experience. Jpn J Clin Oncol. 2005;35:531–5.

    Article  PubMed  Google Scholar 

  23. Boige V, Malka D, Elias D, et al. Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure. Ann Surg Oncol. 2008;15:219–26.

    Article  PubMed  Google Scholar 

  24. Onaitis M, Morse M, Hurwitz H, et al. Adjuvant hepatic arterial chemotherapy following metastasectomy in patients with isolated liver metastases. Ann Surg. 2003;237:782–8.

    Article  PubMed  Google Scholar 

  25. Lien WM, Ackerman NB. The blood supply of experimental liver metastases. II. A microcirculatory study of the normal and tumor vessels of the liver with the use of perfused silicone rubber. Surgery. 1970;68:334–40.

    CAS  PubMed  Google Scholar 

  26. Bower M, Metzger T, Robbins K, et al. Surgical downstaging and neo-adjuvant therapy in metastatic colorectal carcinoma with irinotecan drug-eluting beads: a multi-institutional study. HPB. 2010;12:31–6.

    Google Scholar 

Download references

Conflict of Interest

The research registry reported on herein received support from an unrestricted educational grant from Biocompatibles. R.C.G.M. has served as a consultant for Biocompatibles.

Author information

Authors and Affiliations

  1. Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA

    Robert C. G. Martin PhD & Jonathan Joshi MD

  2. Baptist Health, Little Rock, AR, USA

    Ken Robbins MD

  3. Huntsville Hospital, Huntsville, AL, USA

    Dana Tomalty MD

  4. Institute of Radiology, University Clinical Center, Nis, Serbia

    Petar Bosnjakovik MD

  5. Institute of Clinical and Interventional Radiology, Usti Nad Labem, Czech Republic

    Milous Derner MD

  6. Department of Diagnostic and Interventional Radiology, Institute of Clinical and Interventional Radiology (IKEM), Prague 4, Czech Republic

    Miloslav Rocek MD

  7. Departments of Radiology, Pediatric Hematology, and Oncology, University Hospital Motol and 2nd Medical Faculty, Charles University, Prague, Czech Republic

    Radek Padr MD

  8. Regional Oncological Dispenser, Samara, Russia

    Alexander Scupchenko MD

  9. Norton Radiology, Louisville, KY, USA

    Cliff Tatum MD

Authors
  1. Robert C. G. Martin PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan Joshi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ken Robbins MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dana Tomalty MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Petar Bosnjakovik MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Milous Derner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Radek Padr MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Miloslav Rocek MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alexander Scupchenko MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Cliff Tatum MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert C. G. Martin PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, R.C.G., Joshi, J., Robbins, K. et al. Hepatic Intra-Arterial Injection of Drug-Eluting Bead, Irinotecan (DEBIRI) in Unresectable Colorectal Liver Metastases Refractory to Systemic Chemotherapy: Results of Multi-Institutional Study. Ann Surg Oncol 18, 192–198 (2011). https://doi.org/10.1245/s10434-010-1288-5

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-010-1288-5

Keywords

Search

Navigation