Intra-arterial infusion of 5-fluorouracil plus granulocyte-macrophage colony-stimulating factor (GM-CSF) and chemoembolization with melphalan in the treatment of disseminated colorectal liver metastases

Eur J Surg Oncol. 2001 Nov;27(7):652-61. doi: 10.1053/ejso.2001.1193.


Aims: We compared two prospective trials of intra-arterial cytokine/chemotherapeutic infusion plus chemoembolization in the treatment of inoperable colorectal liver metastases.

Materials and methods: One hundred and three patients with disseminated inoperable colorectal liver metastases received intra-arterial chemotherapy with 5-FU and granulocyte-macrophage colony-stimulating factor (GM-CSF) plus chemoembolization via an angiographically positioned hepatic artery catheter. Two different regimens were used in two consecutive studies. Group A: short-term i.a. infusion of 550 mg/m(2)5-FU (days 1-4) plus 80 microg/m(2)GM-CSF (day 1+2) combined with chemoembolization with 25 mg/m(2)melphalan plus Lipiodol and Gelfoam (day 5). Group B: continuous circadian intra-arterially administered 1400 mg/m(2)5-FU infusion plus 60 mg/m(2)i.v. leucovorin and 80 microg/m(2)GM-CSF (day 1+2) combined with chemoembolization with 25 mg/m(2)melphalan plus Lipiodol and Gelfoam (day 3).

Results: One hundred and three patients (62 male/41 female) with a median age of 59.9 and a median Karnofsky index of 88.5 were treated with 447 cycles of immuno-chemoembolization (group A 299, group B 148 cycles). Fifty-seven percent of these patients had received prior systemic chemotherapy. Side-effects were seen in all patients, mainly upper abdominal pain lasting 1-4 days and grade 1 or 2 vomiting. Systemic side-effects were mild and transient with a very low rate of leukopenia. Using World Health Organization response criteria, the following responses could be demonstrated: group A: CR 2.7%, PR 32.4%, MR 21.6%, SD 12.7%, NR 16.2%; group B: CR 1.0%, PR 42.4%, MR 24.2%, SD 18.2%, NR 12.1%. Time to progression was 7 as compared to 8 months. Median survival was 17 months in group A, whereas it has not been reached after 28 months (P=0.0095) in group B. There was no statistically significant difference between chemo-naive patients and patients who had received prior systemic therapy.

Conclusion: Immuno-chemoembolization combined with 2-day circadian administration of 5-FU is an effective tool in the treatment of disseminated colorectal liver metastases. This regimen is also effective as second-line treatment.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemoembolization, Therapeutic*
  • Colorectal Neoplasms / pathology*
  • Combined Modality Therapy
  • Dendritic Cells / metabolism
  • Female
  • Fluorouracil / administration & dosage
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Humans
  • Infusions, Intravenous
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / therapy*
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Prospective Studies
  • Statistics, Nonparametric
  • Survival Rate


  • Granulocyte Colony-Stimulating Factor
  • Melphalan
  • Fluorouracil