Skip to main content

Advertisement

SpringerLink
Log in

Toxicity of Irinotecan-Eluting Beads in the Treatment of Hepatic Malignancies: Results of a Multi-Institutional Registry

  • Clinical Investigation
  • Published:
CardioVascular and Interventional Radiology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the predictors of toxicity of drug-eluting beads loaded with irinotecan (DEBIRI) in the treatment of hepatic malignancies.

Materials and Methods

A total of 330 patients were enrolled in a prospective, open-label, multicenter, multinational, single-arm study administering two types of drug-eluting beads (DEBIRI and drug-eluting beads loaded with doxorubicin). Complications were graded by Cancer Therapy Evaluation Program’s Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All events requiring additional physician treatment or requiring extended hospital stay or readmission within 30 days were included.

Results

A total of 109 patients received 187 DEBIRI treatments (range 1 to 5 per patient). The most common histology was metastatic colorectal cancer in 76% of patients, cholangiocarcinoma in 7% of patients, and other metastatic disease in 17% of patients. There were 35 patients (19%) with irinotecan treatments who sustained 158 treatment-related adverse events, with the median CTCAE event grade being CTCAE grade 2 (range 1 to 5). The most common adverse events were postembolic symptoms (42%). Multivariate analysis identified pretreatment and treatment-related risk factors as follows: lack of pretreatment with hepatic arterial lidocaine (p = 0.005), ≥3 treatments (p = 0.05), achievement of complete stasis (p = 0.04), treatment with >100 mg DEBIRI in 1 treatment (p = 0.03), and bilirubin >2.0 μg/dl with >50% liver involvement (p = 0.05). These factors were predictive of adverse events and significantly greater hospital length of stay.

Conclusions

DEBIRI is safe when appropriate technique and treatment are used. Adverse events can be predicted based on pretreatment- and treatment-related factors, and their occurrence can become part of the informed consent process. Continued standardization of this treatment will lead to fewer adverse events and improved patient quality of life.

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

Similar content being viewed by others

References

  1. Scoggins CR, Meszoely IM, Blanke CD et al (1999) Nonoperative management of primary colorectal cancer in patients with stage IV disease. Ann Surg Oncol 6:651–657

    Article  CAS  PubMed  Google Scholar 

  2. Martin RC, Robbins K, Tomalty D et al (2009) 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 7:80

    Article  PubMed  Google Scholar 

  3. Aliberti C, Tilli M, Benea G et al (2006) Trans-arterial chemoembolization (TACE) of liver metastases from colorectal cancer using irinotecan-eluting beads: Preliminary results. Anticancer Res 26:3793–3795

    CAS  PubMed  Google Scholar 

  4. Fiorentini G, Aliberti C, Turrisi G et al (2007) Intraarterial hepatic chemoembolization of liver metastases from colorectal cancer adopting irinotecan-eluting beads: results of a phase II clinical study. In Vivo 21:1085–1091

    CAS  PubMed  Google Scholar 

  5. Tang Y, Taylor RR, Gonzalez MV et al (2006) Evaluation of irinotecan drug-eluting beads: a new drug-device combination product for the chemoembolization of hepatic metastases. J Control Release 116:e55–e56

    Article  CAS  PubMed  Google Scholar 

  6. Taylor RR, Tang Y, Gonzalez MV et al (2007) Irinotecan drug eluting beads for use in chemoembolization: in vitro and in vivo evaluation of drug release properties. Eur J Pharm Sci 30:7–14

    Article  CAS  PubMed  Google Scholar 

  7. Xu Y, Villalona-Calero MA (2002) Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity. Ann Oncol 13:1841–1851

    Article  CAS  PubMed  Google Scholar 

  8. Hecht JR (1998) Gastrointestinal toxicity or irinotecan. Oncology (Williston Park) 12:72–78

    CAS  Google Scholar 

  9. Slichenmyer WJ, Rowinsky EK, Donehower RC et al (1993) The current status of camptothecin analogues as antitumor agents. J Natl Cancer Inst 85:271–291

    Article  CAS  PubMed  Google Scholar 

  10. Potmesil M (1994) Camptothecins: from bench research to hospital wards. Cancer Res 54:1431–1439

    CAS  PubMed  Google Scholar 

  11. Hsiang YH, Hertzberg R, Hecht S et al (1985) Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 260:14873–14878

    CAS  PubMed  Google Scholar 

  12. Hsiang YH, Liu LF, Wall ME et al (1989) DNA topoisomerase I-mediated DNA cleavage and cytotoxicity of camptothecin analogues. Cancer Res 49:4385–4389

    CAS  PubMed  Google Scholar 

  13. Jaxel C, Kohn KW, Wani MC et al (1989) Structure-activity study of the actions of camptothecin derivatives on mammalian topoisomerase I: evidence for a specific receptor site and a relation to antitumor activity. Cancer Res 49:1465–1469

    CAS  PubMed  Google Scholar 

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

    Google Scholar 

  15. Lewis AL, Gonzalez MV, Lloyd AW et al (2006) DC bead: in vitro characterization of a drug-delivery device for transarterial chemoembolization. J Vasc Interv Radiol 17:335–342

    Article  PubMed  Google Scholar 

  16. Kaiser J, Thiesen J, Kramer I (2009) Stability of irinotecan-loaded drug eluting beads (DC BeadTM) used for transarterial chemoembolisation. J Oncol Pharm Pract 6:53–61

    Google Scholar 

  17. Morise Z, Sugioka A, Kato R et al (2006) Transarterial chemoembolization with degradable starch microspheres, irinotecan, and mitomycin-C in patients with liver metastases. J Gastrointest Surg 10:249–258

    Article  PubMed  Google Scholar 

  18. Mi Z, Burke TG (1994) Differential interactions of camptothecin lactone and carboxylate forms with human blood components. Biochemistry 33:10325–10336

    Article  CAS  PubMed  Google Scholar 

  19. Mathijssen RH, van Alphen RJ, Verweij J et al (2001) Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res 7:2182–2194

    CAS  PubMed  Google Scholar 

  20. Kunimoto T, Nitta K, Tanaka T et al (1987) Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec, in a novel water-soluble derivative of camptothecin, against murine tumors. Cancer Res 47:5944–5947

    CAS  PubMed  Google Scholar 

  21. Kawato Y, Aonuma M, Hirota Y et al (1991) Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res 51:4187–4191

    CAS  PubMed  Google Scholar 

  22. Burke TG, Munshi CB, Mi Z et al (1995) The important role of albumin in determining the relative human blood stabilities of the camptothecin anticancer drugs. J Pharm Sci 84:518–519

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

Supported by an Unrestricted Educational Grant from Biocompatibles. RCGM: Consultant Biocompatibles.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Surgery, Division of Surgical Oncology, University of Louisville, Louisville, KY, USA

    R. C. G. Martin

  2. North Mississippi Medical Center, Tupelo, MS, USA

    J. Howard

  3. Huntsville Hospital, Huntsville, AL, USA

    D. Tomalty

  4. Baptist Health, Little Rock, AR, USA

    K. Robbins

  5. FN v Motole, Motole, Czech Republic

    R. Padr

  6. Centar Nis Serbia, Nis, Serbia

    P. M. Bosnjakovic

  7. Department of Radiology, Norton Hospital, Louisville, KY, USA

    Cliff Tatum

Authors
  1. R. C. G. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Howard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Tomalty
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K. Robbins
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Padr
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P. M. Bosnjakovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Cliff Tatum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. C. G. Martin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martin, R.C.G., Howard, J., Tomalty, D. et al. Toxicity of Irinotecan-Eluting Beads in the Treatment of Hepatic Malignancies: Results of a Multi-Institutional Registry. Cardiovasc Intervent Radiol 33, 960–966 (2010). https://doi.org/10.1007/s00270-010-9937-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-010-9937-4

Keywords

Search

Navigation