Skip to main content

Advertisement

SpringerLink
Log in

Drug-Eluting Bead, Irinotecan Therapy of Unresectable Intrahepatic Cholangiocarcinoma (DELTIC) with Concomitant Systemic Gemcitabine and Cisplatin

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

Abstract

Background

Unresectable intrahepatic cholangiocarcinoma (ICC) carries a poor prognosis, and currently there are moderately established chemotherapeutic [gemcitabine/cisplatin (Gem/Cis)] treatments to prolong survival. The purpose of this study was to assess the efficacy of irinotecan drug-eluting beads (DEBIRI) therapy by transarterial infusion in combination with systemic therapy in unresectable ICC.

Patients and Methods

This is a prospective, multicenter, open-label, randomized phase II study (Clin Trials: NCT01648023-DELTIC trial) of patients with ICC randomly assigned to Gem/Cis with DEBIRI or Gem/Cis alone. The primary endpoint was response rate.

Results

The intention-to-treat population comprised 48 patients: 24 treated with Gem/Cis and DEBIRI and 22 with Gem/Cis alone (2 screen failures). The two groups were similar with respect to the extent of liver involvement (35% versus 38%) and presence of extrahepatic disease (29% versus 14%, p = 0.12). Median numbers of chemotherapy cycles were similar (6 versus 6), as were rates of grade 3/4 adverse events (34% for the Gem/Cis-DEBIRI group versus 36% for the Gem/Cis group). The overall response rate was significantly greater in the Gem/Cis-DEBIRI arm versus the Gem/Cis arm at 2 (p < 0.04), 4 (p < 0.03), and 6 months (p < 0.05). There was significantly more downsizing to resection/ablation in the Gem/Cis-DEBIRI arm versus the Gem/Cis arm (25% versus 8%, p < 005), and there was improved median progression-free survival [31.9 (95% CI 8.5–75.3) months versus 10.1 (95% CI 5.3–13.5) months, p = 0.028] and improved overall survival [33.7 (95% CI 13.5–54.5) months versus 12.6 (95% CI 8.7–33.4) months, p = 0.048].

Conclusion

Combination Gem/Cis with DEBIRI is safe, and leads to significant improvement in downsizing to resection, improved progression-free survival, and overall survival.

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

Similar content being viewed by others

References

  1. American Cancer Society Cancer Statistics 2021 Report. J Nucl Med. 2021;62(3):12.

  2. Rizvi S, Khan S, Hallemeier C, Kelley R, Gores G. Cholangiocarcinoma—evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15(2):95–111.

    Article  CAS  Google Scholar 

  3. Benson A, D’angelica M, Abbott D, et al. Hepatobiliary cancers, version 2.2021, Nccn clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2021;19(5):541–65.

    Article  Google Scholar 

  4. Valle J, Wasan H, Palmer Dh, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. New Engl J Med. 2010;362(14):1273–81.

    Article  CAS  Google Scholar 

  5. Kato A, Shimizu H, Ohtsuka M, et al. Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study. Ann Surg Oncol. 2013;20(1):318–24.

    Article  Google Scholar 

  6. Lamarca A, Hubner R, David RW, Valle J. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol. 2014;25(12):2328–38.

    Article  CAS  Google Scholar 

  7. Brieau B, Dahan L, De Rycke Y, et al. Second-line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine-platinum combination: a large multicenter study by the Association Des Gastro-Enterologues Oncologues. Cancer. 2015;121(18):3290–7.

    Article  CAS  Google Scholar 

  8. Lamarca A, Palmer D, Wasan H, et al. Second-line folfox chemotherapy versus active symptom control for advanced biliary tract cancer (Abc-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021;22(5):690–701.

    Article  CAS  Google Scholar 

  9. Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with Folfox4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (Eortc Intergroup Trial 40983): a randomised controlled trial. Lancet. 2008;371(9617):1007–16.

    Article  CAS  Google Scholar 

  10. Nakano H, Oussoultzoglou E, Rosso E, et al. Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy. Ann Surg. 2008;247(1):118–24.

    Article  Google Scholar 

  11. Schiffman S, Metzger T, Dubel G, et al. Precision hepatic arterial irinotecan therapy in the treatment of unresectable intrahepatic cholangiocellular carcinoma: optimal tolerance and prolonged overall survival. Ann Surg Oncol. 2011;18(2):431–8.

    Article  Google Scholar 

  12. Martin R, Joshi J, Robbins K, Tomalty D, O’hara R, Tatum C. Transarterial chemoembolization of metastatic colorectal carcinoma with drug-eluting beads, irinotecan (Debiri): multi-institutional registry. J Oncol. 2009;2009:539795.

    Article  Google Scholar 

  13. Martin R, 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. 2011;18(1):192–8.

    Article  Google Scholar 

  14. Martin R, 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(1):80.

    Article  Google Scholar 

  15. Martin R, Scoggins C, Tomalty D, et al. Irinotecan drug-eluting beads in the treatment of chemo-naive unresectable colorectal liver metastasis with concomitant systemic fluorouracil and oxaliplatin: results of pharmacokinetics and phase I trial. J Gastrointest Surg. 2012;24:2012.

    Google Scholar 

  16. Hyder O, Marsh J, Salem R, et al. Intra-arterial therapy for advanced intrahepatic cholangiocarcinoma: a multi-institutional analysis. Ann Surg Oncol. 2013;20(12):3779–86.

    Article  Google Scholar 

  17. Seidensticker R, Seidensticker M, Doegen K, et al. Extensive use of interventional therapies improves survival in unresectable or recurrent intrahepatic cholangiocarcinoma. Gastroenterol Res Pract. 2016;2016:8732521.

    Article  Google Scholar 

  18. Martin R, Scoggins C, Schreeder M, et al. Randomized controlled trial of irinotecan drug-eluting beads with simultaneous folfox and bevacizumab for patients with unresectable colorectal liver-limited metastasis. Cancer. 2015;6:2015.

    Google Scholar 

  19. Eisenhauer E, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised recist guideline (Version 1.1). Eur J Cancer. 2009;45(2):228–47.

    Article  CAS  Google Scholar 

  20. Chung W, Park M, Shin S, et al. Response evaluation in patients with colorectal liver metastases: recist version 1.1 versus modified ct criteria. Am J Roentgenol. 2012;199(4):809–15.

    Article  Google Scholar 

  21. Choi H, Charnsangavej C, Faria S, 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(13):1753–9.

    Article  Google Scholar 

  22. Rc Martin, Cr Scoggins, Km Mcmasters. Microwave hepatic ablation: initial experience of safety and efficacy. J Surg Oncol. 2007;96(6):481–6.

    Article  Google Scholar 

  23. Rc Martin, Cr Scoggins, Km Mcmasters. Safety and efficacy of microwave ablation of hepatic tumors: a prospective review of a 5-year experience. Ann Surg Oncol. 2010;17(1):171–8.

    Article  Google Scholar 

  24. Schiffman S, Metzger T, Dubel G, et al. Precision hepatic arterial irinotecan therapy in the treatment of unresectable intrahepatic cholangiocellular carcinoma: optimal tolerance and prolonged overall survival. Ann Surg Oncol. 2010;2:10.

    Google Scholar 

  25. Edeline J, Touchefeu Y, Guiu B, et al. Radioembolization plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2020;6(1):51–9.

    Article  Google Scholar 

  26. Aida T, Furukawa K, Suzuki D, et al. Preoperative immunonutrition decreases postoperative complications by modulating prostaglandin E2 production and T-cell differentiation in patients undergoing pancreatoduodenectomy. Surgery. 2014;155(1):124–33.

    Article  Google Scholar 

  27. Savic L, Chapiro J, Geschwind J. Intra-arterial embolotherapy for intrahepatic cholangiocarcinoma: update and future prospects. Hepatobiliary Surg Nutr. 2017;6(1):7–21.

    Article  Google Scholar 

  28. Mondaca S, Yarmohammadi H, Kemeny N. Regional chemotherapy for biliary tract tumors and hepatocellular carcinoma. Surg Oncol Clin N Am. 2019;28(4):717–29.

    Article  Google Scholar 

  29. Martin R, Howard J, Tomalty D, et al. Toxicity of irinotecan-eluting beads in the treatment of hepatic malignancies: results of a multi-institutional registry. Cardiovasc Interv Radiol. 2010;33(5):960–6.

    Article  CAS  Google Scholar 

  30. Lencioni R, Aliberti C, De Baere T, et al. Transarterial treatment of colorectal cancer liver metastases with irinotecan-loaded drug-eluting beads: technical recommendations. J Vasc Interv Radiol. 2014;25(3):365–9.

    Article  Google Scholar 

Download references

Acknowledgements

A special thanks to all the patients and research coordinators who put their heart and soul into this trial and completion.

Funding

University of Louisville Division of Surgical Oncology. FDA: IDE Submission # NCT01648023.

Author information

Authors and Affiliations

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

    Robert C. G. Martin II MD, PhD, FACS, Prejesh Philips MD, Kelly M. McMasters MD, PhD & Charles R. Scoggins MD, MBA

  2. James Graham Brown Cancer Center Louisville, Louisville, KY, USA

    Robert C. G. Martin II MD, PhD, FACS, Prejesh Philips MD, Kelly M. McMasters MD, PhD, Vivek R. Sharma MD & Charles R. Scoggins MD, MBA

  3. ProMedica Physicians Hepatobiliary and Pancreatic Surgery, Toledo University, Toledo, OH, USA

    Kerri A. Simo MD

  4. Providence Health and Services, Portland, OR, USA

    Paul Hansen MD & Todd S. Crocenzi MD

  5. Virginia Mason Medical Center, Seattle, WA, USA

    Flavio Rocha MD

  6. Norton Hospital Radiology Associates, Louisville, KY, USA

    Clifton M. Tatum MD & Lawrence R. Kelly MD

  7. Norton Cancer Institute, Louisville, KY, USA

    Michael Driscoll MD

Authors
  1. Robert C. G. Martin II MD, PhD, FACS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kerri A. Simo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul Hansen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Flavio Rocha MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Prejesh Philips MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kelly M. McMasters MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Clifton M. Tatum MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lawrence R. Kelly MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael Driscoll MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Vivek R. Sharma MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Todd S. Crocenzi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Charles R. Scoggins MD, MBA
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert C. G. Martin II MD, PhD, FACS.

Ethics declarations

Disclosure

Partial funding for this trial came from both BTG/Biocompatibles and Boston Scientific. None of the authors have conflicts to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Martin, R.C.G., Simo, K.A., Hansen, P. et al. Drug-Eluting Bead, Irinotecan Therapy of Unresectable Intrahepatic Cholangiocarcinoma (DELTIC) with Concomitant Systemic Gemcitabine and Cisplatin. Ann Surg Oncol 29, 5462–5473 (2022). https://doi.org/10.1245/s10434-022-11932-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-022-11932-3

Search

Navigation