Floxuridine hepatic arterial infusion associated biliary toxicity is increased by concurrent administration of systemic bevacizumab Journal Article


Authors: Cercek, A.; D'Angelica, M.; Power, D.; Capanu, M.; Gewirtz, A.; Patel, D.; Allen, P.; Fong, Y.; DeMatteo, R. P.; Jarnagin, W. R.; Kemeny, N. E.
Article Title: Floxuridine hepatic arterial infusion associated biliary toxicity is increased by concurrent administration of systemic bevacizumab
Abstract: Purpose: Systemic bevacizumab (Bev) was added to hepatic arterial infusion (HAI) floxuridine (FUDR)-based chemotherapy in three studies in an attempt to improve outcomes. A specific review of biliary toxicity was carried out. Methods: This analysis included 203 patients from three prospective studies. The first (study A) was an adjuvant study after liver resection of colorectal metastases in which patients received HAI and systemic chemotherapy (Sys) with or without Bev. Study B comprised unresectable colorectal patients who received HAI and Sys plus Bev. Study C included patients with unresectable cholangiocarcinoma or hepatocellular carcinoma who received HAI plus systematic Bev. The outcome and toxicity of patients in studies B and C were compared with historical controls. Results: In all three studies, the incidence of hyperbilirubinemia and biliary stent placement within 1 year of treatment was increased with the addition of Bev. In the no-Bev versus Bev groups, the placement of biliary stents was as follows: study A, 0 of 38 versus 4 of 35 patients (p = 0.05); study B, 0 of 49 versus 3 of 24 (p = 0.06); and study C, 0 of 34 versus 3 of 22 (p = 0.15). Elevation in bilirubin was noted in the no-Bev versus Bev groups: study A, 0 of 38 versus 5 of 35 patients (p = 0.02); study B, 1 of 49 versus 7 of 24 (p = 0.005); and study C, 2 of 34 versus 5 of 22 (p = 0.10). The addition of Bev did not seem to be associated with improved progression-free or overall survival. Conclusions: The addition of Bev to HAI FUDR resulted in increased biliary toxicity in three separate studies. Although the sample sizes were small, there was no evidence of improved PFS or OS with the addition of Bev. Bev should not be combined with HAI FUDR. © 2013 Society of Surgical Oncology.
Keywords: overall survival; bevacizumab; liver cell carcinoma; progression free survival; bilirubin; liver metastasis; liver resection; bile duct carcinoma; hyperbilirubinemia; inoperable cancer; floxuridine; bilirubin blood level; randomized controlled trial (topic); phase 2 clinical trial (topic); drug intoxication; colorectal liver metastasis; biliary stent; human; article
Journal Title: Annals of Surgical Oncology
Volume: 21
Issue: 2
ISSN: 1068-9265
Publisher: Springer  
Date Published: 2014-02-01
Start Page: 479
End Page: 486
Language: English
DOI: 10.1245/s10434-013-3275-0
PROVIDER: scopus
PUBMED: 24154839
DOI/URL:
Notes: Export Date: 2 April 2014 -- CODEN: ASONF -- Source: Scopus
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MSK Authors
  1. Ronald P DeMatteo
    637 DeMatteo
  2. Marinela Capanu
    386 Capanu
  3. Peter Allen
    501 Allen
  4. William R Jarnagin
    905 Jarnagin
  5. Derek Gerard Power
    38 Power
  6. Yuman Fong
    775 Fong
  7. Nancy Kemeny
    544 Kemeny
  8. Alexandra Gewirtz
    21 Gewirtz
  9. Dina Patel
    7 Patel