Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver

Michael J. O'Connell, David M. Nagorney, Albert M. Bernath, Georgene Schroeder, Robert Joseph Fitzgibbons, James A. Mailliard, Patrick Burch, John S. Bolton, Gerardo Colon-Otero, James E. Krook

Research output: Contribution to journalArticle

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Abstract

Purpose: Extrahepatic metastasis represents a frequent pattern of disease progression when fluorodeoxyuridine (FUDR) is given by the intraarterial route for the treatment of unresectable colorectal liver metastases. Systemic fluorouracil (5-FU) plus leucovorin was added to introhepatic FUDR to prolong the duration of disease control. Methods: Only patients with colorectal cancer who had evidence of unresectable metastases confined to the liver were eligible. Laparotomy was performed to establish arterial perfusion of the liver. Cycles of intrahepatic FUDR followed by a 1- week rest period then intravenous chemotherapy with 5-FU plus leucovorin were administered until maximal regression of hepatic metastases. Maintenance chemotherapy with 5-FU plus leucovorin was then given until disease progression. Results: Fifty-seven patients entered this trial; four patients (7%) were ineligible and 13 (23%) did not receive any chemotherapy on study because of findings at laparotomy. The 40 eligible patients who began chemotherapy are included in the statistical analyses. Twenty-five patients (62% of those who received chemotherapy) experienced regression of liver metastases. The median time to tumor progression was 9 months, but only 3% remained pregression-free at 24 months. The median survival duration was 18 months. Toxicity was tolerable with no cases of biliary sclerosis. One treatment-related fatality due to sepsis was observed. Conclusion: Although short-term treatment results appear to be somewhat better than we have previously observed with intrahepatic FUDR alone, the sequential regimen did not have on impact on long-term, progression-free survival in patients with unresectable liver metastases. We are now investigating this regimen as surgical adjuvant therapy in selected patients following hepatic metastasectomy where this aggressive approach might have a greater therapeutic effect in the minimal residual disease setting.

Original languageEnglish
Pages (from-to)2528-2533
Number of pages6
JournalJournal of Clinical Oncology
Volume16
Issue number7
StatePublished - Jul 1998
Externally publishedYes

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Floxuridine
Leucovorin
Fluorouracil
Colorectal Neoplasms
Neoplasm Metastasis
Liver
Drug Therapy
Laparotomy
Therapeutics
Disease Progression
Maintenance Chemotherapy
Metastasectomy
Residual Neoplasm
Sclerosis
Therapeutic Uses
Disease-Free Survival
Sepsis
Perfusion
Survival

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver. / O'Connell, Michael J.; Nagorney, David M.; Bernath, Albert M.; Schroeder, Georgene; Fitzgibbons, Robert Joseph; Mailliard, James A.; Burch, Patrick; Bolton, John S.; Colon-Otero, Gerardo; Krook, James E.

In: Journal of Clinical Oncology, Vol. 16, No. 7, 07.1998, p. 2528-2533.

Research output: Contribution to journalArticle

O'Connell, MJ, Nagorney, DM, Bernath, AM, Schroeder, G, Fitzgibbons, RJ, Mailliard, JA, Burch, P, Bolton, JS, Colon-Otero, G & Krook, JE 1998, 'Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver', Journal of Clinical Oncology, vol. 16, no. 7, pp. 2528-2533.
O'Connell, Michael J. ; Nagorney, David M. ; Bernath, Albert M. ; Schroeder, Georgene ; Fitzgibbons, Robert Joseph ; Mailliard, James A. ; Burch, Patrick ; Bolton, John S. ; Colon-Otero, Gerardo ; Krook, James E. / Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver. In: Journal of Clinical Oncology. 1998 ; Vol. 16, No. 7. pp. 2528-2533.
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title = "Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver",
abstract = "Purpose: Extrahepatic metastasis represents a frequent pattern of disease progression when fluorodeoxyuridine (FUDR) is given by the intraarterial route for the treatment of unresectable colorectal liver metastases. Systemic fluorouracil (5-FU) plus leucovorin was added to introhepatic FUDR to prolong the duration of disease control. Methods: Only patients with colorectal cancer who had evidence of unresectable metastases confined to the liver were eligible. Laparotomy was performed to establish arterial perfusion of the liver. Cycles of intrahepatic FUDR followed by a 1- week rest period then intravenous chemotherapy with 5-FU plus leucovorin were administered until maximal regression of hepatic metastases. Maintenance chemotherapy with 5-FU plus leucovorin was then given until disease progression. Results: Fifty-seven patients entered this trial; four patients (7{\%}) were ineligible and 13 (23{\%}) did not receive any chemotherapy on study because of findings at laparotomy. The 40 eligible patients who began chemotherapy are included in the statistical analyses. Twenty-five patients (62{\%} of those who received chemotherapy) experienced regression of liver metastases. The median time to tumor progression was 9 months, but only 3{\%} remained pregression-free at 24 months. The median survival duration was 18 months. Toxicity was tolerable with no cases of biliary sclerosis. One treatment-related fatality due to sepsis was observed. Conclusion: Although short-term treatment results appear to be somewhat better than we have previously observed with intrahepatic FUDR alone, the sequential regimen did not have on impact on long-term, progression-free survival in patients with unresectable liver metastases. We are now investigating this regimen as surgical adjuvant therapy in selected patients following hepatic metastasectomy where this aggressive approach might have a greater therapeutic effect in the minimal residual disease setting.",
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T1 - Sequential intrahepatic fluorodeoxyuridine and systemic fluorouracil plus leucovorin for the treatment of metastatic colorectal cancer confined to the liver

AU - O'Connell, Michael J.

AU - Nagorney, David M.

AU - Bernath, Albert M.

AU - Schroeder, Georgene

AU - Fitzgibbons, Robert Joseph

AU - Mailliard, James A.

AU - Burch, Patrick

AU - Bolton, John S.

AU - Colon-Otero, Gerardo

AU - Krook, James E.

PY - 1998/7

Y1 - 1998/7

N2 - Purpose: Extrahepatic metastasis represents a frequent pattern of disease progression when fluorodeoxyuridine (FUDR) is given by the intraarterial route for the treatment of unresectable colorectal liver metastases. Systemic fluorouracil (5-FU) plus leucovorin was added to introhepatic FUDR to prolong the duration of disease control. Methods: Only patients with colorectal cancer who had evidence of unresectable metastases confined to the liver were eligible. Laparotomy was performed to establish arterial perfusion of the liver. Cycles of intrahepatic FUDR followed by a 1- week rest period then intravenous chemotherapy with 5-FU plus leucovorin were administered until maximal regression of hepatic metastases. Maintenance chemotherapy with 5-FU plus leucovorin was then given until disease progression. Results: Fifty-seven patients entered this trial; four patients (7%) were ineligible and 13 (23%) did not receive any chemotherapy on study because of findings at laparotomy. The 40 eligible patients who began chemotherapy are included in the statistical analyses. Twenty-five patients (62% of those who received chemotherapy) experienced regression of liver metastases. The median time to tumor progression was 9 months, but only 3% remained pregression-free at 24 months. The median survival duration was 18 months. Toxicity was tolerable with no cases of biliary sclerosis. One treatment-related fatality due to sepsis was observed. Conclusion: Although short-term treatment results appear to be somewhat better than we have previously observed with intrahepatic FUDR alone, the sequential regimen did not have on impact on long-term, progression-free survival in patients with unresectable liver metastases. We are now investigating this regimen as surgical adjuvant therapy in selected patients following hepatic metastasectomy where this aggressive approach might have a greater therapeutic effect in the minimal residual disease setting.

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