title: Hepatic arterial chemotherapy in combination with systemic chemotherapy compared with hepatic arterial chemotherapy alone for liver metastases from colorectal cancer: results of a multi-centric randomized study.
abstract: Hepatic arterial infusion (HAI) chemotherapy is accepted to be an option in patients with non-resectable metastases from colorectal cancer confined to the liver. In a multi-istitutional trial, 76 patients were randomly assigned to receive HAI versus HAI plus systemic bolus 5-fluorouracil and leucovorin. The primary endpoint was survival, followed by response, recurrence and toxicity. Survival was longer for HAI plus systemic chemotherapy (HAI+SYC) than HAI (median, 20 vs. 14 months; p = 0.0033), as were responses (47.5% and 41.7%; p = 0.09) and time to hepatic progression (12 vs. 8 months; p = 0.039). Side effects included haematological toxicity that was mostly mild and reversible in 432 cases. Neutropenia grade 3 occurred in four patients in the HAI+SYC arm and one in the HAI arm. Diarrhoea occurred in 20% and 7% of patients and stomatitis occurred in 18% and 2%, respectively. On the contrary biliary toxicity was significant; twelve patients had evidence of bilirubin elevations of more than 3 mg/dl (six in each arm), and two had asymptomatic arterial biliary-tree fistulae: one in the HAI+SYC arm and one in the HAI arm. Grade 3 elevation in alkaline phosphatase and aminotransferase levels occurred in 26% and 24%, respectively. In conclusion, the combination of HAI+SYC is active and safe showing a clinical advantage with respect to simple HAI, increasing overall survival, response rate and time to progression.
authors.affiliation: Department of Oncology and Surgical Oncology, "S. Giuseppe" General Hospital, Empoli (Florence), Italy. oncologiaempoli@usl11.toscana.it
authors.forename: Giammaria
authors.initials: G
authors.lastname: Fiorentini
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cantore
authors.forename: Susanna
authors.initials: S
authors.lastname: Rossi
authors.forename: Marco
authors.initials: M
authors.lastname: Vaira
authors.forename: Salvatore
authors.initials: S
authors.lastname: Tumolo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Dentico
authors.forename: Andrea
authors.initials: A
authors.lastname: Mambrini
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernardeschi
authors.forename: Gina
authors.initials: G
authors.lastname: Turrisi
authors.forename: Petros
authors.initials: P
authors.lastname: Giovanis
authors.forename: Stefano
authors.initials: S
authors.lastname: Guadagni
authors.forename: Vanna
authors.initials: V
authors.lastname: Valori
authors.forename: Michele
authors.initials: M
authors.lastname: De Simone
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004338:Drug Combinations; D005467:Floxuridine / Q000008:administration & dosage*; D005472:Fluorouracil / Q000008:administration & dosage*; D006499:Hepatic Artery; D006801:Humans; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D005467:Floxuridine; D002955:Leucovorin; D005472:Fluorouracil