Advertisement

Cancer Chemotherapy and Pharmacology

, Volume 82, Issue 5, pp 877–885 | Cite as

A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without intravenous bevacizumab, in patients with advanced cancer and predominant liver involvement

  • Elena Fountzilas
  • Elangovan Krishnan
  • Filip Janku
  • Siqing Fu
  • Daniel D. Karp
  • Aung Naing
  • Vivek Subbiah
  • David S. Hong
  • Sarina A. Piha-Paul
  • David J. Vining
  • Apostolia-Maria Tsimberidou
Original Article
  • 144 Downloads

Abstract

Background

We investigated hepatic arterial infusion (HAI) oxaliplatin combined with capecitabine +/− bevacizumab in advanced cancer with predominant liver involvement.

Methods

Patients received HAI oxaliplatin (140 mg/m2) and escalating doses of capecitabine (500, 750, and 1000 mg/m2), with (Group 1) or without (Group 2) bevacizumab (10 mg/kg IV). A 3 + 3 dose design was used, followed by an expansion phase.

Results

From 9/2009 to 2/2014, 61 patients (34 men, 27 women) were enrolled (Group 1 = 44; Group 2 = 17). Patients were treated in Group 2 if they had contraindications to bevacizumab (n = 13) or if there was no opening in Group 1 (n = 4). The median age was 60 years (range, 20–88). The most common cancers were colorectal (22 patients), liver (12), pancreatic (7), breast (4), and biliary tract (4). The median number of prior therapies was 3 (range, 1–12); 32 (53%) patients had received oxaliplatin. The dose-limiting toxicity was Grade 3 diarrhea and occurred in 2 patients receiving 1000 mg/m2 capecitabine. The maximum tolerated dose was HAI oxaliplatin 140 mg/m2, capecitabine 750 mg/m2, and bevacizumab 10 mg/kg. The most common toxicities were nausea/vomiting, anemia, thrombocytopenia, neutropenia, and hypomagnesemia. The rates of partial response and stable disease ≥ 4 months were 22% and 39% (Group 1) and 9% and 0% (Group 2). The respective median time to treatment failure and overall survival were 3 and 6.9 months (Group 1) and 1.5 and 5.9 months (Group 2).

Conclusion

HAI oxaliplatin combined with capecitabine +/− bevacizumab was well-tolerated and was associated with favorable outcomes in selected patients.

Keywords

Bevacizumab Capecitabine Dose-limiting toxicity Hepatic arterial infusion Maximum tolerated dose Oxaliplatin 

Notes

Acknowledgements

Dr. Fountzilas has received a scholarship from the Hellenic Society of Medical Oncology (10/2017-09/2018).

Funding

NIH/NCI, award number P30 CA016672.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest for this manuscript.

References

  1. 1.
    Yoo TG, Cranshaw I, Broom R, Pandanaboyana S, Bartlett A (2017) Systematic review of early and long-term outcome of liver resection for metastatic breast cancer: Is there a survival benefit? Breast 32:162–172CrossRefGoogle Scholar
  2. 2.
    Agarwala SS, Eggermont AM, O’Day S, Zager JS (2014) Metastatic melanoma to the liver: a contemporary and comprehensive review of surgical, systemic, and regional therapeutic options. Cancer 120:781–789CrossRefGoogle Scholar
  3. 3.
    Weiser MR, Jarnagin WR, Saltz LB (2013) Colorectal cancer patients with oligometastatic liver disease: what is the optimal approach? Oncology (Williston Park) 27:1074–1078Google Scholar
  4. 4.
    Barber FD, Mavligit G, Kurzrock R (2004) Hepatic arterial infusion chemotherapy for metastatic colorectal cancer: a concise overview. Cancer Treat Rev 30:425–436CrossRefGoogle Scholar
  5. 5.
    Song MJ (2015) Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma. World J Gastroenterol 21:3843–3849CrossRefGoogle Scholar
  6. 6.
    Tewes M, Peis MW, Bogner S et al (2017) Hepatic arterial infusion chemotherapy for extensive liver metastases of breast cancer: efficacy, safety and prognostic parameters. J Cancer Res Clin Oncol 143:2131–2141CrossRefGoogle Scholar
  7. 7.
    Tsimberidou AM, Letourneau K, Fu S et al (2011) Phase I clinical trial of hepatic arterial infusion of paclitaxel in patients with advanced cancer and dominant liver involvement. Cancer Chemother Pharmacol 68:247–253CrossRefGoogle Scholar
  8. 8.
    Tsimberidou AM, Moulder S, Fu S et al (2010) Phase I clinical trial of hepatic arterial infusion of cisplatin in combination with intravenous liposomal doxorubicin in patients with advanced cancer and dominant liver involvement. Cancer Chemother Pharmacol 66:1087–1093CrossRefGoogle Scholar
  9. 9.
    Tsimberidou AM, Ye Y, Wheler J et al (2013) A phase I study of hepatic arterial infusion of nab-paclitaxel in combination with intravenous gemcitabine and bevacizumab for patients with advanced cancers and predominant liver metastases. Cancer Chemother Pharmacol 71:955–963CrossRefGoogle Scholar
  10. 10.
    Tsimberidou AM, Fu S, Ng C et al (2010) A phase 1 study of hepatic arterial infusion of oxaliplatin in combination with systemic 5-fluorouracil, leucovorin, and bevacizumab in patients with advanced solid tumors metastatic to the liver. Cancer 116:4086–4094CrossRefGoogle Scholar
  11. 11.
    Tsimberidou AM, Leick MB, Lim J et al (2013) Dose-finding study of hepatic arterial infusion of oxaliplatin-based treatment in patients with advanced solid tumors metastatic to the liver. Cancer Chemother Pharmacol 71:389–397CrossRefGoogle Scholar
  12. 12.
    Said R, Kurzrock R, Naing A et al (2015) Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver. Invest New Drugs 33:911–920CrossRefGoogle Scholar
  13. 13.
    Tsimberidou AM, Vaklavas C, Fu S et al (2013) Hepatic arterial infusion therapy in advanced cancer and liver-predominant disease: the MD Anderson Experience. Hepatogastroenterology 60:1611–1623PubMedGoogle Scholar
  14. 14.
    Hainsworth JD, Spigel DR, Burris HA 3rd et al (2010) Oxaliplatin and capecitabine in the treatment of patients with recurrent or refractory carcinoma of unknown primary site: a phase 2 trial of the Sarah Cannon Oncology Research Consortium. Cancer 116:2448–2454PubMedGoogle Scholar
  15. 15.
    Cassidy J, Clarke S, Diaz-Rubio E et al (2008) Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 26:2006–2012CrossRefGoogle Scholar
  16. 16.
    Tebbutt NC, Wilson K, Gebski VJ et al (2010) Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol 28:3191–3198CrossRefGoogle Scholar
  17. 17.
    Cunningham D, Lang I, Marcuello E et al (2013) Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 14:1077–1085CrossRefGoogle Scholar
  18. 18.
    Chen YX, Yang Q, Kuang JJ et al (2014) Efficacy of adding bevacizumab in the first-line chemotherapy of metastatic colorectal cancer: evidence from seven randomized clinical trials. Gastroenterol Res Pract 2014:594930PubMedPubMedCentralGoogle Scholar
  19. 19.
    Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefGoogle Scholar
  20. 20.
    Kemeny N, Jarnagin W, Paty P et al (2005) Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol 23:4888–4896CrossRefGoogle Scholar
  21. 21.
    Liu W, Song QK, Xing BC (2015) A systematic review and meta-analysis to reappraise the role of adjuvant hepatic arterial infusion for colorectal cancer liver metastases. Int J Colorectal Dis 30:1091–1102CrossRefGoogle Scholar
  22. 22.
    Kemeny NE, Niedzwiecki D, Hollis DR et al (2006) Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481). J Clin Oncol 24:1395–1403CrossRefGoogle Scholar
  23. 23.
    Ducreux M, Ychou M, Laplanche A et al (2005) Hepatic arterial oxaliplatin infusion plus intravenous chemotherapy in colorectal cancer with inoperable hepatic metastases: a trial of the gastrointestinal group of the Federation Nationale des Centres de Lutte Contre le Cancer. J Clin Oncol 23:4881–4887CrossRefGoogle Scholar
  24. 24.
    Boige V, Malka D, Elias D et al (2008) Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure. Ann Surg Oncol 15:219–226CrossRefGoogle Scholar
  25. 25.
    Goere D, Deshaies I, de Baere T et al (2010) Prolonged survival of initially unresectable hepatic colorectal cancer patients treated with hepatic arterial infusion of oxaliplatin followed by radical surgery of metastases. Ann Surg 251:686–691CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Elena Fountzilas
    • 1
  • Elangovan Krishnan
    • 1
  • Filip Janku
    • 1
  • Siqing Fu
    • 1
  • Daniel D. Karp
    • 1
  • Aung Naing
    • 1
  • Vivek Subbiah
    • 1
  • David S. Hong
    • 1
  • Sarina A. Piha-Paul
    • 1
  • David J. Vining
    • 2
  • Apostolia-Maria Tsimberidou
    • 1
  1. 1.Department of Investigational Cancer Therapeutics, Unit 455The University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Diagnostic RadiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations