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


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.


CONCLUSIONS
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.
Müller
H
H
Department of Surgical Oncology, Carl von Hess Hospital, D-97762 Hammelburg, Germany. H.Mueller@Klinik-Hammelburg.de
Nakchbandi
W
W
Chatzissavvidis
I
I
Valek
V
V
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016461:Chemoembolization, Therapeutic; D015179:Colorectal Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D015996:Survival Rate
D016179:Granulocyte Colony-Stimulating Factor; D008558:Melphalan; D005472:Fluorouracil