Assessment of hepatic arterial infusion of floxuridine in combination with systemic gemcitabine and oxaliplatin in patients with unresectable intrahepatic cholangiocarcinoma: A phase 2 clinical trial Journal Article


Authors: Cercek, A.; Boerner, T.; Tan, B. R.; Chou, J. F.; Gönen, M.; Boucher, T. M.; Hauser, H. F.; Do, R. K. G.; Lowery, M. A.; Harding, J. J.; Varghese, A. M.; Reidy-Lagunes, D.; Saltz, L.; Schultz, N.; Kingham, T. P.; D'Angelica, M. I.; Dematteo, R. P.; Drebin, J. A.; Allen, P. J.; Balachandran, V. P.; Lim, K. H.; Sanchez-Vega, F.; Vachharajani, N.; Majella Doyle, M. B.; Fields, R. C.; Hawkins, W. G.; Strasberg, S. M.; Chapman, W. C.; Diaz, L. A. Jr; Kemeny, N. E.; Jarnagin, W. R.
Article Title: Assessment of hepatic arterial infusion of floxuridine in combination with systemic gemcitabine and oxaliplatin in patients with unresectable intrahepatic cholangiocarcinoma: A phase 2 clinical trial
Abstract: Importance: Unresectable intrahepatic cholangiocarcinoma (IHC) carries a poor prognosis, with a median overall survival (OS) of 11 months. Hepatic arterial infusion (HAI) of high-dose chemotherapy may have potential benefit in these patients. Objective: To evaluate clinical outcomes when HAI chemotherapy is combined with systemic chemotherapy in patients with unresectable IHC. Design, Setting, and Participants: A single-institution, phase 2 clinical trial including 38 patients was conducted with HAI floxuridine plus systemic gemcitabine and oxaliplatin in patients with unresectable IHC at Memorial Sloan Kettering Cancer Center between May 20, 2013, and June 27, 2019. A confirmatory phase 1/2 study using the same therapy was conducted during the same time period at Washington University in St Louis. Patients with histologically confirmed, unresectable IHC were eligible. Resectable metastatic disease to regional lymph nodes and prior systemic therapy were permitted. Patients with distant metastatic disease were excluded. Interventions: Hepatic arterial infusion of floxuridine and systemic administration of gemcitabine and oxaliplatin. Main Outcomes and Measures: The primary outcome was progression-free survival (PFS) of 80% at 6 months. Results: For the phase 2 clinical trial at Memorial Sloan Kettering Cancer Center, 42 patients with unresectable IHC were included and, of these, 38 patients were treated (13 [34%] men; median [range] age at diagnosis, 64 [39-81] years). The median follow-up was 30.5 months. Twenty-two patients (58%) achieved a partial radiographic response, and 32 patients (84%) achieved disease control at 6 months. Four patients had sufficient response to undergo resection, and 1 patient had a complete pathologic response. The median PFS was 11.8 months (1-sided 90% CI, 11.1) with a 6-month PFS rate of 84.1% (90% CI, 74.8%-infinity), thereby meeting the primary end point (6-month PFS rate, 80%). The median OS was 25.0 months (95% CI, 20.6-not reached), and the 1-year OS rate was 89.5% (95% CI, 80.2%-99.8%). Patients with resectable regional lymph nodes (18 [47%]) showed no difference in OS compared with patients with node-negative disease (24-month OS: lymph node negative: 60%; 95% CI, 40%-91% vs lymph node positive: 50%; 95% CI, 30%-83%; P =.66). Four patients (11%) had grade 4 toxic effects requiring removal from the study (1 portal hypertension, 2 gastroduodenal artery aneurysms, 1 infection in the pump pocket). Subgroup analysis showed significant improvement in survival in patients with IDH1/2 mutated tumors (2-year OS, 90%; 95% CI, 73%-99%) vs wild-type (2-year OS, 33%; 95% CI, 18%-63%) (P =.01). In the Washington University in St Louis confirmatory cohort, 9 patients (90%) achieved disease control at 6 months; the most common grade 3 toxic effect was elevated results of liver function tests, and median PFS was 12.8 months (1-sided 90% CI, 6.4). Conclusions and Relevance: Hepatic arterial infusion plus systemic chemotherapy appears to be highly active and tolerable in patients with unresectable IHC; further evaluation is warranted. © 2019 American Medical Association. All rights reserved.
Keywords: adult; cancer survival; clinical article; treatment outcome; treatment response; aged; survival rate; overall survival; fatigue; histopathology; ascites; cancer combination chemotherapy; dose response; drug withdrawal; side effect; gemcitabine; follow up; lymph node metastasis; progression free survival; infection; multiple cycle treatment; phase 2 clinical trial; nausea; thrombocytopenia; hemoglobin; age; abdominal pain; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; survival time; albumin; glucose blood level; bile duct carcinoma; cancer control; oxaliplatin; portal hypertension; floxuridine; sodium; lymphocyte; phosphate; amylase; potassium; platelet count; triacylglycerol lipase; isocitrate dehydrogenase 1; aneurysm; isocitrate dehydrogenase 2; human; male; female; article; gastroduodenal artery aneurysm
Journal Title: JAMA Oncology
Volume: 6
Issue: 1
ISSN: 2374-2437
Publisher: American Medical Association  
Date Published: 2020-01-01
Start Page: 60
End Page: 67
Language: English
DOI: 10.1001/jamaoncol.2019.3718
PUBMED: 31670750
PROVIDER: scopus
PMCID: PMC6824231
DOI/URL:
Notes: Article -- Export Date: 3 February 2020 -- Source: Scopus
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MSK Authors
  1. Joanne Fu-Lou Chou
    335 Chou
  2. Leonard B Saltz
    792 Saltz
  3. Mithat Gonen
    1033 Gonen
  4. James Joseph Harding
    254 Harding
  5. Anna Mary Varghese
    146 Varghese
  6. Diane Lauren Reidy
    295 Reidy
  7. Maeve Aine Lowery
    133 Lowery
  8. William R Jarnagin
    910 Jarnagin
  9. Kinh Gian Do
    260 Do
  10. T Peter Kingham
    619 Kingham
  11. Nancy Kemeny
    545 Kemeny
  12. Nikolaus D Schultz
    491 Schultz
  13. Taryn Mary Boucher
    16 Boucher
  14. Jeffrey Adam Drebin
    168 Drebin
  15. Luis Alberto Diaz
    153 Diaz
  16. Thomas Boerner
    72 Boerner
  17. Haley Frances Hauser
    18 Hauser