Skip to main content
Top
Published in: Annals of Surgical Oncology 1/2008

01-01-2008 | Gastrointestinal Oncology

Hepatic Arterial Infusion of Oxaliplatin and Intravenous LV5FU2 in Unresectable Liver Metastases from Colorectal Cancer after Systemic Chemotherapy Failure

Authors: Valérie Boige, MD, David Malka, MD, PhD, Dominique Elias, MD, PhD, Marine Castaing, MS, Thierry De Baere, MD, Diane Goere, MD, Clarisse Dromain, MD, Marc Pocard, MD, PhD, Michel Ducreux, MD, PhD

Published in: Annals of Surgical Oncology | Issue 1/2008

Login to get access

Abstract

Background

We have previously shown promising activity of hepatic arterial infusion (HAI) oxaliplatin combined with intravenous (IV) 5-fluorouracil (5-FU) and leucovorin (LV) as first-line chemotherapy in patients with colorectal liver metastases (CRLM) (intent-to-treat [ITT] objective response rate [ORR], 64%; secondary resection rate, 18%; overall survival [OS], 27 months). Whether this regimen could be beneficial after systemic chemotherapy failure is unknown.

Methods

Patients with unresectable CRLM and history of systemic chemotherapy failure were treated bimonthly with HAI oxaliplatin (100 mg/m2 2 hours) combined with IV LV and IV bolus and infusional 5FU (modified LV5FU2 regimen).

Results

Forty-four consecutive patients (median age 56 years; median number of prior systemic chemotherapy regimens, 2 range 1–5) were included, of whom 43 (98%) had previously received oxaliplatin (n = 34), irinotecan (n = 37), or both (n = 28). Patients received a median of nine cycles of HAI oxaliplatin and IV modified LV5FU2 (range 0–25). Toxicity included grade 3–4 neutropenia (43%), grade 2–3 neuropathy (43%), and grade 3–4 abdominal pain (14%). We observed 24 partial ORs (62%) among the 39 assessable patients (ITT ORR, 55%; 95% CI, 40–69%), including 17, 12, and 12 patients who had failed to respond to prior systemic chemotherapy with FOLFIRI, FOLFOX, or both, respectively. Tumor response allowed further R0 surgical resection (n = 7) or radiofrequency ablation (n = 1) of initially unresectable CRLM in eight patients (18%). Median progression-free survival and OS were 7 and 16 months, respectively.

Conclusions

HAI oxaliplatin and IV LV5FU2 is feasible, safe, and shows promising activity after systemic chemotherapy failure, allowing surgical resection of initially unresectable CRLM in 18% of patients.
Literature
1.
go back to reference Breedis C, Young C. The blood supply of neoplasm in the liver. Am J Pathol 1954; 30:969–74PubMed Breedis C, Young C. The blood supply of neoplasm in the liver. Am J Pathol 1954; 30:969–74PubMed
2.
go back to reference Chen GHG, Gross JF. Intra-arterial infusion of anticancer drugs: theoretic aspects of drug delivery and review of responses. Cancer Treat Rep 1980; 64:31–40PubMed Chen GHG, Gross JF. Intra-arterial infusion of anticancer drugs: theoretic aspects of drug delivery and review of responses. Cancer Treat Rep 1980; 64:31–40PubMed
3.
go back to reference Meta-Analysis group in Cancer. Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. J Natl Cancer Inst 1996; 88:252–8CrossRef Meta-Analysis group in Cancer. Reappraisal of hepatic arterial infusion in the treatment of nonresectable liver metastases from colorectal cancer. J Natl Cancer Inst 1996; 88:252–8CrossRef
4.
go back to reference Kerr DJ, McArdle CS, Ledermann J, et al. Intrahepatic arterial versus intravenous fluorouracil and folinic acid for colorectal cancer liver metastases: a multicentre randomised trial. Lancet 2003; 361:368–73PubMedCrossRef Kerr DJ, McArdle CS, Ledermann J, et al. Intrahepatic arterial versus intravenous fluorouracil and folinic acid for colorectal cancer liver metastases: a multicentre randomised trial. Lancet 2003; 361:368–73PubMedCrossRef
5.
go back to reference Tournigand C, André T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22:229–37PubMedCrossRef Tournigand C, André T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22:229–37PubMedCrossRef
6.
go back to reference Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22:23–30PubMedCrossRef Goldberg RM, Sargent DJ, Morton RF, et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22:23–30PubMedCrossRef
7.
go back to reference Colucci G, Gebbia V, Paoletti G, et al. Phase III randomised trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell’Italia Meridionale. J Clin Oncol 2005; 23:4866–75PubMedCrossRef Colucci G, Gebbia V, Paoletti G, et al. Phase III randomised trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell’Italia Meridionale. J Clin Oncol 2005; 23:4866–75PubMedCrossRef
8.
go back to reference Köhne CH, van Cutsem E, Wils J, et al. Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986. J Clin Oncol 2005; 23:4856–65PubMedCrossRef Köhne CH, van Cutsem E, Wils J, et al. Phase III study of weekly high-dose infusional fluorouracil plus folinic acid with or without irinotecan in patients with metastatic colorectal cancer: European Organisation for Research and Treatment of Cancer Gastrointestinal Group Study 40986. J Clin Oncol 2005; 23:4856–65PubMedCrossRef
9.
go back to reference Rothenberg ML, Oza AM, Bigelow RH, et al. Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial. J Clin Oncol 2003; 21:2059–69PubMedCrossRef Rothenberg ML, Oza AM, Bigelow RH, et al. Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial. J Clin Oncol 2003; 21:2059–69PubMedCrossRef
10.
go back to reference Ulrich-Pur H, Kornek GV, Fiebiger W, et al. Multicenter phase II trial of dose-fractionated irinotecan in patients with advanced colorectal cancer failing oxaliplatin-based first-line combination chemotherapy. Ann Oncol 2001; 12:1269–72PubMedCrossRef Ulrich-Pur H, Kornek GV, Fiebiger W, et al. Multicenter phase II trial of dose-fractionated irinotecan in patients with advanced colorectal cancer failing oxaliplatin-based first-line combination chemotherapy. Ann Oncol 2001; 12:1269–72PubMedCrossRef
11.
go back to reference Park SH, Sung JY, Han SH, et al. Oxaliplatin, folinic acid and 5-fluorouracil (FOLFOX-4) combination chemotherapy as second-line treatment in advanced colorectal cancer patients with irinotecan failure: a Korean single-center experience. Jpn J Clin Oncol 2005; 35:531–5PubMedCrossRef Park SH, Sung JY, Han SH, et al. Oxaliplatin, folinic acid and 5-fluorouracil (FOLFOX-4) combination chemotherapy as second-line treatment in advanced colorectal cancer patients with irinotecan failure: a Korean single-center experience. Jpn J Clin Oncol 2005; 35:531–5PubMedCrossRef
12.
go back to reference Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351:337–45PubMedCrossRef Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004; 351:337–45PubMedCrossRef
13.
go back to reference Kemeny NE, Niedzwiecki D, Hollis DR, et al. 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 2006; 24:1395–1403PubMedCrossRef Kemeny NE, Niedzwiecki D, Hollis DR, et al. 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 2006; 24:1395–1403PubMedCrossRef
14.
go back to reference 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; 23:4881–7PubMedCrossRef 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; 23:4881–7PubMedCrossRef
15.
go back to reference Conroy T, Gory-Delabaere G, Adenis A, et al. Clinical practice guideline: (2003) update of Standards, Options et Recommendations for first line palliative chemotherapy in patients with metastatic colorectal cancer (summary report). Bull Cancer 2004; 91:759–68PubMed Conroy T, Gory-Delabaere G, Adenis A, et al. Clinical practice guideline: (2003) update of Standards, Options et Recommendations for first line palliative chemotherapy in patients with metastatic colorectal cancer (summary report). Bull Cancer 2004; 91:759–68PubMed
16.
go back to reference Levi F, Perpoint B, Garufi C, et al. Oxaliplatin activity against metastatic colorectal cancer. A phase II study of 5-day continuous venous infusion at circadian rhythm modulated rate. Eur J Cancer 1993; 29A:1280–4PubMedCrossRef Levi F, Perpoint B, Garufi C, et al. Oxaliplatin activity against metastatic colorectal cancer. A phase II study of 5-day continuous venous infusion at circadian rhythm modulated rate. Eur J Cancer 1993; 29A:1280–4PubMedCrossRef
17.
go back to reference WHO Handbook for Reporting Results of Cancer Treatment. World Health Organization, Geneva, Switzerland, 1979 WHO Handbook for Reporting Results of Cancer Treatment. World Health Organization, Geneva, Switzerland, 1979
18.
go back to reference Simon R. Optimal two-stage designs for phase II clinical trials in oncology. Control Clin Trials 1989; 10:1–10PubMedCrossRef Simon R. Optimal two-stage designs for phase II clinical trials in oncology. Control Clin Trials 1989; 10:1–10PubMedCrossRef
19.
go back to reference Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Statist Assoc 1958; 53:457–81CrossRef Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Statist Assoc 1958; 53:457–81CrossRef
20.
go back to reference Kemeny N, Jarnagin W, Paty P, et al. Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol 2005; 23:4888–96PubMedCrossRef Kemeny N, Jarnagin W, Paty P, et al. Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol 2005; 23:4888–96PubMedCrossRef
21.
go back to reference Kemeny N, Gonen M, Sullivan D, et al. Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. J Clin Oncol 2001; 19:2687–95PubMed Kemeny N, Gonen M, Sullivan D, et al. Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. J Clin Oncol 2001; 19:2687–95PubMed
22.
go back to reference Rougier P, Laplanche A, Huguier M, et al. Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial. J Clin Oncol 1992; 10:1112–8PubMed Rougier P, Laplanche A, Huguier M, et al. Hepatic arterial infusion of floxuridine in patients with liver metastases from colorectal carcinoma: long-term results of a prospective randomized trial. J Clin Oncol 1992; 10:1112–8PubMed
23.
go back to reference Kern W, Beckert B, Lang N, et al. Phase I and pharmacokinetic study of hepatic arterial infusion with oxaliplatin in combination with folinic acid and 5-fluorouracil in patients with hepatic metastases from colorectal cancer. Ann Oncol 2001; 12:599–603PubMedCrossRef Kern W, Beckert B, Lang N, et al. Phase I and pharmacokinetic study of hepatic arterial infusion with oxaliplatin in combination with folinic acid and 5-fluorouracil in patients with hepatic metastases from colorectal cancer. Ann Oncol 2001; 12:599–603PubMedCrossRef
24.
go back to reference Dzodic R, Gomez-Abuin G, Rougier P, et al. Pharmacokinetic advantage of intra-arterial hepatic oxaliplatin administration: comparative results with cisplatin using a rabbit VX2 tumor model. Anticancer Drugs 2004; 15:647–50PubMedCrossRef Dzodic R, Gomez-Abuin G, Rougier P, et al. Pharmacokinetic advantage of intra-arterial hepatic oxaliplatin administration: comparative results with cisplatin using a rabbit VX2 tumor model. Anticancer Drugs 2004; 15:647–50PubMedCrossRef
25.
go back to reference van Riel JM, van Groeningen CJ, Kedde MA, et al. Continuous administration of irinotecan by hepatic arterial infusion: a phase I and pharmacokinetic study. Clin Cancer Res 2002; 8:405–12PubMed van Riel JM, van Groeningen CJ, Kedde MA, et al. Continuous administration of irinotecan by hepatic arterial infusion: a phase I and pharmacokinetic study. Clin Cancer Res 2002; 8:405–12PubMed
26.
go back to reference van Riel JM, van Groeningen CJ, de Greve J, Gruia G, Pinedo HM, Giaccone G. Continuous infusion of hepatic arterial irinotecan in pretreated patients with colorectal cancer metastatic to the liver. Ann Oncol 2004; 15:59–63PubMedCrossRef van Riel JM, van Groeningen CJ, de Greve J, Gruia G, Pinedo HM, Giaccone G. Continuous infusion of hepatic arterial irinotecan in pretreated patients with colorectal cancer metastatic to the liver. Ann Oncol 2004; 15:59–63PubMedCrossRef
27.
go back to reference Mancuso A, Giuliani R, Accettura C, et al. Hepatic arterial continuous infusion (HACI) of oxaliplatin in patients with unresectable liver metastases from colorectal cancer. Anticancer Res 2003; 23:1917–22PubMed Mancuso A, Giuliani R, Accettura C, et al. Hepatic arterial continuous infusion (HACI) of oxaliplatin in patients with unresectable liver metastases from colorectal cancer. Anticancer Res 2003; 23:1917–22PubMed
28.
go back to reference Aldrighetti L, Arru M, Angeli E, et al. Percutaneous versus surgical placement of hepatic artery indwelling catheters for regional chemotherapy. Hepatogastroenterology 2002; 49:513–7PubMed Aldrighetti L, Arru M, Angeli E, et al. Percutaneous versus surgical placement of hepatic artery indwelling catheters for regional chemotherapy. Hepatogastroenterology 2002; 49:513–7PubMed
Metadata
Title
Hepatic Arterial Infusion of Oxaliplatin and Intravenous LV5FU2 in Unresectable Liver Metastases from Colorectal Cancer after Systemic Chemotherapy Failure
Authors
Valérie Boige, MD
David Malka, MD, PhD
Dominique Elias, MD, PhD
Marine Castaing, MS
Thierry De Baere, MD
Diane Goere, MD
Clarisse Dromain, MD
Marc Pocard, MD, PhD
Michel Ducreux, MD, PhD
Publication date
01-01-2008
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 1/2008
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-007-9581-7

Other articles of this Issue 1/2008

Annals of Surgical Oncology 1/2008 Go to the issue