title: A phase I study of continuous hepatic arterial infusion of Irinotecan in patients with locally advanced hepatocellular carcinoma.
abstract: OBJECTIVE
  Aim of this phase I study was to identify the maximum tolerated dose and dose limiting toxicity of continuous infusion of Irinotecan through a port-a-cath placed in the hepatic artery in patients with hepatocellular carcinoma and cirrhosis to explore new strategies in advanced hepatocellular carcinoma. Response rate and time-to-progression were analysed.
  
  
  METHODS
  Irinotecan was delivered as a five-day continuous infusion every 21 days, with increases of 2.5mg/m(2)/day every three patients, starting from 7.5mg/m(2)/day. Dose limiting toxicity corresponded to one patient in each triplet developing G4 haematological or G3 non-haematological toxicity, confirmed in two triplets. Twenty-eight patients (17 Child-Pugh A, 11 B) received treatment and tumour response was assessed after three courses completed by 22 patients.
  
  
  RESULTS
  Dose limiting toxicity was G3 diarrhoea in two patients, reached at 27.5mg/m(2)/day and the recommended dose was set at 25mg/m(2)/day. Nineteen of 30 patients experienced adverse events related to porth-a-cath placement and one died from liver ischemia and sepsis. Median time-to-progression was 11.3 months.
  
  
  CONCLUSIONS
  Intrarterial infusion of Irinotecan is feasible in patients with hepatocellular carcinoma on cirrhosis at a recommended dose of 25mg/m(2)/day, with no major adverse drug-related events, but with some concerns about the insertion and management of the intra-arterial device.
authors.affiliation: Seràgnoli Department of Haematology and Oncological Sciences, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy. giovanni.brandi@unibo.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Brandi
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Mirarchi
authors.forename: Rita
authors.initials: R
authors.lastname: Golfieri
authors.forename: Antonello
authors.initials: A
authors.lastname: Di Paolo
authors.forename: Alberto
authors.initials: A
authors.lastname: Borghi
authors.forename: Silvia
authors.initials: S
authors.lastname: Fanello
authors.forename: Enrico
authors.initials: E
authors.lastname: Derenzini
authors.forename: Valentina
authors.initials: V
authors.lastname: Agostini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Giampalma
authors.forename: Alberta
authors.initials: A
authors.lastname: Cappelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pini
authors.forename: Sarah
authors.initials: S
authors.lastname: Costantini
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Luigi
authors.initials: L
authors.lastname: Bolondi
authors.forename: Fabio
authors.initials: F
authors.lastname: Piscaglia
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002404:Catheterization / Q000009:adverse effects; D003967:Diarrhea / Q000209:etiology; D018572:Disease-Free Survival; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin