Skip to main content
SpringerLink
Log in

Switching the Loaded Agent from Epirubicin to Cisplatin: Salvage Transcatheter Arterial Chemoembolization with Drug-eluting Microspheres for Unresectable Hepatocellular Carcinoma

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

Abstract

Purpose

There is no consensus on switching anticancer agents loaded onto drug carriers in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). This study aimed to evaluate the safety and clinical outcomes of TACE with cisplatin-loaded microspheres (CLM-TACE) in HCC patients refractory to TACE with epirubicin-loaded microspheres (ELM-TACE).

Methods

Between February 2008 and June 2010, 85 patients with unresectable HCC refractory to ELM-TACE were enrolled to undergo CLM-TACE. The number of ELM-TACE sessions until judgment of resistance ranged from 1 to 4 (median, 2.1). CLM-TACE was performed using 50–100-μm superabsorbent polymer microspheres loaded with 1 mg cisplatin/1 mg microspheres together with hepatic arterial infusion of 25 mg cisplatin and 500 mg 5-fluorouracil per patient. Tumor responses were evaluated by computed tomography according to the European Association for the Study of the Liver criteria.

Results

The median number of CLM-TACE treatment sessions was 1.8 (range, 1–5), and the mean total dose of cisplatin per session was 42.8 mg (range, 30.0–59.0). After 6 months, 3 (3.5%) patients achieved complete response, 31 (36.5%) had partial response, 15 (17.6%) had stable disease, and 36 (42.4%) had progressive disease. The median overall survival and time to treatment failure after initial CLM-TACE were 13.3 and 7.2 months, respectively. Overall, 9.4% of patients experienced grade 3/4 adverse events.

Conclusion

Switching the loaded agent from epirubicin to cisplatin is a safe, well-tolerated, and efficacious treatment strategy for salvage TACE with drug-eluting microspheres in HCC patients refractory to ELM-TACE.

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. El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576

    Article  PubMed  CAS  Google Scholar 

  2. Cottone M, Turri M, Caltagirone M et al (1988) Early detection of hepatocellular carcinoma associated with cirrhosis by ultrasound and alfafetoprotein: a prospective study. Hepatogastroenterology 35:101–103

    PubMed  CAS  Google Scholar 

  3. Bruix J, Sherman M, Llovet JM et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 35:421–430

    Article  PubMed  CAS  Google Scholar 

  4. Llovet JM, Bruix J (2003) Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival. Hepatology 37:429–442

    Article  PubMed  CAS  Google Scholar 

  5. Llovet JM, Real MI, Montana X et al (2002) Arterial embolization or chemoembolization versus systemic treatment in patients with unresectable hepatocellular carcinoma: a randomized controlled trial. Lancet 359:1734–1739

    Article  PubMed  Google Scholar 

  6. Marelli L, Stigliano R, Triantos C et al (2007) Transarterial therapy for hepatocellular carcinoma: which technique is more effective? A systematic review of cohort and randomized studies. Cardiovasc Intervent Radiol 30:6–25

    Article  PubMed  Google Scholar 

  7. Yamada R, Sato M, Kawabata M et al (1983) Hepatic artery embolization in 120 patients with unresectable hepatoma. Radiology 148:397–401

    PubMed  CAS  Google Scholar 

  8. Brown DB, Cardella JF, Sacks D et al (2009) Quality improvement guidelines for transhepatic arterial chemoembolization, embolization, and chemotherapeutic infusion for hepatic malignancy. J Vasc Interv Radiol 20(Suppl 7):S219–S226

    Article  PubMed  Google Scholar 

  9. Satake M, Uchida H, Arai Y et al (2008) Transcatheter arterial chemoembolization (TACE) with lipiodol to treat hepatocellular carcinoma: survey results from the TACE study group of Japan. Cardiovasc Intervent Radiol 31:756–761

    Article  PubMed  Google Scholar 

  10. Sonomura T, Yamada R, Kishi K et al (1997) Dependency of tissue necrosis on gelatin sponge particle size after canine hepatic artery embolization. Cardiovasc Intervent Radiol 20:50–53

    Article  PubMed  CAS  Google Scholar 

  11. Varela M, Real MI, Burrel M et al (2007) Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics. J Hepatol 46:474–481

    Article  PubMed  CAS  Google Scholar 

  12. Hong K, Khwaja A, Liapi E et al (2006) New intra-arterial drug delivery system for the treatment of liver cancer: preclinical assessment in a rabbit model of liver cancer. Clin Cancer Res 12:2563–2567

    Article  PubMed  CAS  Google Scholar 

  13. 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 

  14. Jordan O, Denys A, De Baere T et al (2010) Comparative study of chemoembolization loadable beads: in vitro drug release and physical properties of DC bead and hepasphere loaded with doxorubicin and irinotecan. J Vasc Interv Radiol 21:1084–1090

    Article  PubMed  Google Scholar 

  15. Maeda N, Osuga K, Higashihara H et al (2010) In vitro characterization of cisplatin-loaded superabsorbent polymer microspheres designed for chemoembolization. J Vasc Interv Radiol 21:877–881

    Article  PubMed  Google Scholar 

  16. Grosso M, Vignali C, Quaretti P et al (2008) Transarterial chemoembolization for hepatocellular carcinoma with drug-eluting microspheres: preliminary results from an Italian multicenter study. Cardiovasc Intervent Radiol 31:1141–1149

    Article  PubMed  Google Scholar 

  17. Seki A, Hori S, Kobayashi K et al (2010) Transcatheter arterial chemoembolization with epirubicin-loaded superabsorbent polymer microspheres for 135 hepatocellular carcinoma patients: single-center experience. Cardiovasc Intervent Radiol. doi:10.1007/s00270-010-9975-y

  18. Poggi G, Amatu A, Montagna B et al (2009) OEM-TACE: a new therapeutic approach in unresectable intrahepatic cholangiocarcinoma. Cardiovasc Intervent Radiol 32:1187–1192

    Article  PubMed  Google Scholar 

  19. Osuga K, Hori S, Hiraishi K et al (2008) Bland embolization of hepatocellular carcinoma using superabsorbent polymer microspheres. Cardiovasc Intervent Radiol 31:1108–1116

    Article  PubMed  Google Scholar 

  20. Yoshikawa M, Ono N, Yodono H et al (2008) Phase II study of hepatic arterial infusion of a fine-powder formulation of cisplatin for advanced hepatocellular carcinoma. Hepatol Res 38:474–483

    Article  PubMed  CAS  Google Scholar 

  21. Maeda N, Osuga K, Mikami K et al (2008) Angiographic evaluation of hepatic arterial damage after transarterial chemoembolization for hepatocellular carcinoma. Radiat Med 26:206–212

    Article  PubMed  Google Scholar 

  22. Lacouture ME, Maitland ML, Segaert S et al (2010) A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer 18:509–522

    Article  PubMed  Google Scholar 

  23. Kalayci C, Johnson PJ, Raby N et al (1990) Intraarterial adriamycin and lipiodol for inoperable hepatocellular carcinoma: a comparison with intravenous adriamycin. J Hepatol 11:349–353

    Article  PubMed  CAS  Google Scholar 

  24. Arora AS, de Groen PC, Croall DE et al (1996) Hepatocellular carcinoma cells resist necrosis during anoxia by preventing phospholipase-mediated calpain activation. J Cell Physiol 167:434–442

    Article  PubMed  CAS  Google Scholar 

  25. Chang JM, Tzeng WS, Pan HB et al (1994) Transcatheter arterial embolization with or without cisplatin treatment of hepatocellular carcinoma. A randomized controlled study. Cancer 74:2449–2453

    Article  PubMed  CAS  Google Scholar 

  26. Kawai S, Okamura J, Ogawa M et al (1992) Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma: a comparison of lipiodol-transcatheter arterial embolization with and without Adriamycin (first cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan. Cancer Chemother Pharmacol 31(suppl):S1–S6

    Article  PubMed  Google Scholar 

  27. Sahara S, Kawai N, Sato M et al (2010) Prospective comparison of transcatheter arterial chemoembolization with Lipiodol–epirubicin and Lipiodol–cisplatin for treatment of recurrent hepatocellular carcinoma. Jpn J Radiol 28:362–368

    Article  PubMed  CAS  Google Scholar 

  28. Kawai S, Tani M, Okamura J et al (1997) Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan. Semin Oncol 24(2 suppl 6):S6-38–S6-45

    Google Scholar 

  29. Nicolini A, Martinetti L, Crespi S et al (2010) Transarterial chemoembolization with epirubicin-eluting beads versus transarterial embolization before liver transplantation for hepatocellular carcinoma. J Vasc Interv Radiol 21:327–332

    Article  PubMed  Google Scholar 

  30. Shen DW, Akiyama S, Schoenlein P et al (1995) Characterisation of high-level cisplatin-resistant cell lines established from a human hepatoma cell line and human KB adenocarcinoma cells: cross-resistance and protein changes. Br J Cancer 71:676–683

    Article  PubMed  CAS  Google Scholar 

  31. Moriguchi M, Takayama T, Nakamura M et al (2010) Phase I/II study of a fine-powder formulation of cisplatin for transcatheter arterial chemoembolization in hepatocellular carcinoma. Hepatol Res 40:369–375

    Article  PubMed  CAS  Google Scholar 

  32. Kawaoka T, Aikata H, Takaki S et al (2009) Transarterial infusion chemotherapy using cisplatin-lipiodol suspension with or without embolization for unresectable hepatocellular carcinoma. Cardiovasc Intervent Radiol 32:687–694

    Article  PubMed  Google Scholar 

  33. Lammer J, Malagari K, Vogl T et al (2010) Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. Cardiovasc Intervent Radiol 33:41–52

    Article  PubMed  Google Scholar 

  34. Kawamura Y, Ikeda K, Hirakawa M et al (2009) Efficacy of platinum analogue for advanced hepatocellular carcinoma unresponsive to transcatheter arterial chemoembolization with epirubicin. Hepatol Res 39:346–354

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Radiology, Gate Tower Institute for Image Guided Therapy, 11F, Gate Tower Building, 1-Rinku Ohrai-Kita, Izumisanocity, Osaka, 598-0048, Japan

    Akihiko Seki & Shinich Hori

Authors
  1. Akihiko Seki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shinich Hori
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akihiko Seki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seki, A., Hori, S. Switching the Loaded Agent from Epirubicin to Cisplatin: Salvage Transcatheter Arterial Chemoembolization with Drug-eluting Microspheres for Unresectable Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 35, 555–562 (2012). https://doi.org/10.1007/s00270-011-0176-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00270-011-0176-0

Keywords

Search

Navigation