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
Müller, H.; Nakchbandi, V.; Chatzisavvidis, I.; von Voigt, C.
Hepato-Gastroenterology 50(54): 1919-1926
2003
ISSN/ISBN: 0172-6390 PMID: 14696433 Document Number: 557950
Background/Aims: 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. Methodology: 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 1400mg/m2 5-FU administered intra-arterially in a continuous circadian mode, 60mg/m2 Rescuvolin given i.v. as a 2-hour infusion, 80mug/m2 GM-CSF given i.a. as a 1-hour infusion, day 3 chemoembolization with 25mg/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.