title: A phase I study of hyperthermic isolated hepatic perfusion with oxaliplatin in the treatment of unresectable liver metastases from colorectal cancer.
abstract: Isolated hepatic perfusion (IHP) is a proven approach for regional delivery of chemotherapy in patients with unresectable primary and metastatic tumors of the liver. Most trials of IHP have utilized melphalan as the active drug in the perfusate. We performed a phase I trial to evaluate the efficacy, safety, and maximum tolerated dose (MTD) of oxaliplatin delivered by hyperthermic isolated hepatic perfusion. A phase I dose-escalation trial of hyperthermic IHP with oxaliplatin in patients with unresectable metastatic colorectal cancer scheduled to undergo placement of a hepatic arterial infusion (HAI) pump was carried out. Thirteen patients were enrolled between November 2003 and September 2006. Dose-limiting veno-occlusive disease was observed at 60 mg/m(2). At the MTD of 40 mg/m(2) only minor transient liver dysfunction was observed. Ultrafilterable platinum area under the curve and maximum concentration delivered by IHP increased nonlinearly with dose as did platinum concentrations in liver biopsies obtained at the end of the 60 min IHP. Seventy-seven percent of patients had a >50% decrease in serum carcinoembryonic antigen (CEA) after IHP. The overall response rate to the combined IHP and HAI therapy was 66%. One patient had a durable complete response (>4 years). We conclude that hyperthermic IHP with oxaliplatin was safe and feasible at a dose of 40 mg/m(2). The ability to obtain complete vascular isolation with open IHP was confirmed. The response rate in this small phase I study was encouraging.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, PA 15232, USA. zehh@upmc.edu
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.forename: Charles K
authors.initials: CK
authors.lastname: Brown
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Holtzman
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
authors.forename: Julianne L
authors.initials: JL
authors.lastname: Holleran
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Potter
authors.forename: David L
authors.initials: DL
authors.lastname: Bartlett
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000032:analysis; D010478:Chemotherapy, Cancer, Regional Perfusion; D015179:Colorectal Neoplasms / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D008207:Lymphatic Metastasis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000077150:Oxaliplatin; D011379:Prognosis; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin