Advertisement

Annals of Surgical Oncology

, Volume 23, Issue 11, pp 3699–3708 | Cite as

Safety and Feasibility of Repeatable Hepatic Vascular Isolation Chemotherapy: A Pilot Study

  • Rodney J. LaneEmail author
  • Nyan Y. Khin
  • Chris M. Rogan
  • John Magnussen
  • Nick Pavlakis
  • David M. Lane
  • Stephen Clarke
Hepatobiliary Tumors

Abstract

Background

The authors herein describe a novel method of repeatable hepatic isolation using an implantable access system allowing simultaneous control of hepatic arterial and portal flows by multiple endovascular catheters.

Purpose

The aim of this study was to assess the feasibility and safety of the system and to compress standard intravenous chemotherapy into 4 weeks of targeted intra-arterial delivery.

Methods

An arterial access system was implanted to the axillary artery via an anastomosis. Infusions of oxaliplatin were performed biweekly for 4 weeks, using balloon catheters to achieve hepatic isolation and segmental selectivity for 20–25 min. Fifty-seven treatments under general anesthetic were performed in ten patients with inoperable chemotherapy-refractory metastatic colorectal cancer. Systemic, intrahepatic, and hepatic venous pressures were recorded to assess vascular isolation, and platinum levels were measured to assess chemotherapy distribution.

Results

Pressure verified, multiple day-only hepatic vascular isolation infusions were achieved in nine of ten patients, with a single patient receiving multiple hepatic arterial infusions. Positron emission tomography–computed tomography (PET–CT) imaging confirmed partial response in three of ten patients and stable disease in three of ten patients. Systemic toxicity was minimal as all treatment-related gastrointestinal and neuropathic symptoms reported throughout the 4 weeks were grades 1–2.

Conclusions

Intra-arterial chemotherapy infusions with hepatic vascular isolation can be achieved repeatedly with targeted selectivity and minimal complications using an implantable multicatheter access system. Oxaliplatin infusions over a 4-week period may achieve tumor response in selected patients in the salvage setting. The technique should be further assessed in a phase Ib/II study.

Keywords

Hepatic Artery Oxaliplatin Tace Rivaroxaban Colorectal Liver Metastasis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

The authors would like to acknowledge Cook Medical for advice and catheter supply, Professor Michael Roberts for advice on pharmacokinetics, and Carol Bryant for infrastructure support.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.CrossRefPubMedGoogle Scholar
  2. 2.
    Leporrier J, Maurel J, Chiche L, Bara S, Segol P, Launoy G. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br J Surg. 2006;93(4):465–74.CrossRefPubMedGoogle Scholar
  3. 3.
    Dexiang Z, Li R, Ye W, et al. Outcome of patients with colorectal liver metastasis: analysis of 1,613 consecutive cases. Ann Surg Oncol. 2012;19(9):2860–68.CrossRefPubMedGoogle Scholar
  4. 4.
    Gibbs P, Heinemann V, Sharma NK, et al. SIRFLOX: randomized phase III trial comparing first-line mFOLFOX6 ± bevacizumab (bev) versus mFOLFOX6 + selective internal radiation therapy (SIRT) ± bev in patients (pts) with metastatic colorectal cancer (mCRC). J Clin Oncol. 2015;33(15 Suppl):abstract 3502.Google Scholar
  5. 5.
    Ducreux M, Ychou M, Laplanche A, et al. 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. 2005;23(22):4881–87.CrossRefPubMedGoogle Scholar
  6. 6.
    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(1):219–26.CrossRefGoogle Scholar
  7. 7.
    D’Angelica MI, Correa-Gallego C, Paty PB, et al. Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer. Ann Surg. 2015;261(2):353–60.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Clavien PA, Yadav S, Sindram D, Bentley RC. Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans. Ann Surg. 2000;232(2):155–62.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Vollmar B, Menger MD. The hepatic microcirculation: mechanistic contributions and therapeutic targets in liver injury and repair. Physiol Rev. 2009;89(4):1269–339.CrossRefPubMedGoogle Scholar
  10. 10.
    Graham MA, Lockwood GF, Greenslade D, Brienza S, Bayssas M, Gamelin E. Clinical pharmacokinetics of oxaliplatin: a critical review. Clin Cancer Res. 2000;6(4):1205–18.PubMedGoogle Scholar
  11. 11.
    Pendyala L, Creaven PJ, Oxaliplatin B. In vitro cytotoxicity, protein binding, red blood cell partitioning, and biotransformation of oxaliplatin. Cancer Res. 1993;53(24):5970–76.PubMedGoogle Scholar
  12. 12.
    Khin NY, Dijkstra ML, Huckson M, et al. Hypertensive extracorporeal limb perfusion for critical limb ischemia. J Vasc Surg. 2013;58(5):1244–53.CrossRefPubMedGoogle Scholar
  13. 13.
    Lane RJ, Phillips M, McMillan D, Huckson M, Liang SWU, Cuzzilla M. Hypertensive extracorporeal limb perfusion (HELP): a new technique for managing critical lower limb ischemia. J Vasc Surg. 2008;48(5):1156–65.CrossRefPubMedGoogle Scholar
  14. 14.
    Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50 Suppl 1:122S–50S.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365–6.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Rodney J. Lane
    • 1
    • 2
    • 3
    • 4
    Email author
  • Nyan Y. Khin
    • 2
    • 4
  • Chris M. Rogan
    • 1
  • John Magnussen
    • 1
    • 2
  • Nick Pavlakis
    • 3
  • David M. Lane
    • 4
  • Stephen Clarke
    • 3
  1. 1.Macquarie University HospitalSydneyAustralia
  2. 2.Australian School of Advanced MedicineMacquarie UniversitySydneyAustralia
  3. 3.The Royal North Shore HospitalSt Leonards, SydneyAustralia
  4. 4.AllVascular Pty LtdSt Leonards, SydneyAustralia

Personalised recommendations