Repetitive chemoembolization with melphalan plus intra-arterial immuno-chemotherapy within 5-fluorouracil and granulocyte-macrophage colony-stimulating factor (GM-CSF) as effective first- and second-line treatment of disseminated colorectal liver metastases.
OBJECTIVE
In order to improve local and systemic efficacy of chemotherapeutic interventions we have used a combination of high concentrated plus low continuous regional chemotherapy modulated by GM-CSF cytokine in the treatment of inoperable colorectal liver metastases.


METHODS
Sixty-six patients with disseminated inoperable colorectal liver metastases received continuous intra-arterial chemotherapy with 5-FU plus GM-CSF short time application plus chemoembolization Melphalan via an angiographically positioned hepatic artery catheter. The regimen consisted of the following steps: On day 1 + 2 1400 mg/m2 5-FU administered intra-arterially in a continuous circadian mode, 60 mg/m2 Rescuvolin given i.v. as a 2-hour infusion, 80 micrograms/m2 GM-CSF given i.a. as a 1-hour infusion, day 3 chemoembolization with 25 mg/m2 Melphalan plus Lipiodol and Gelfoam.


RESULTS
66 patients (38 male/28 female) with a median age of 60.4 years and a median Karnofsky index of 87.3 were treated with 299 cycles of immunochemoembolization. Fifty-four percent of these patients had received prior systemic chemotherapy. Side effects were manifested in all patients, mainly upper abdominal pain lasting one to four 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 CR 1.0%, PR 42.4%, MR 24.2%, SD 18.2%, NR 12.1%. Time to progression was 8 months. Median survival has not been reached after an observation time of 28 months. Two-year survival was 66%. There was no statistically significant difference between chemonaive patients and patients pretreated by any kind of systemic therapy.


CONCLUSIONS
Repetitive high concentrated regional chemotherapy by use of chemoembolization combined with continuous administered 5-FU and supplemented with GM-CSF is an effective tool in the therapy of disseminated colorectal liver metastases as front line as well as a second-line treatment.
Müller
H
H
Department of Oncologic Surgery, Carl von Hess-Hospital, D-97762 Hammelburg, Germany. H.Mueller@Klinik-Hammelburg.de
Nakchbandi
V
V
Chatzisavvidis
I
I
von Voigt
C
C
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D016461:Chemoembolization, Therapeutic / Q000379:methods*; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology / Q000556:secondary* / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008558:Melphalan; D002955:Leucovorin; D005472:Fluorouracil