title: Isolated hepatic perfusion with oxaliplatin combined with 100 mg melphalan in patients with metastases confined to the liver: A phase I study.
abstract: OBJECTIVE
  To improve isolated hepatic perfusion (IHP), we performed a phase I dose-escalation study to determine the optimal oxaliplatin dose in combination with a fixed melphalan dose.
  
  
  METHODS
  Between June 2007 and July 2008, 11 patients, comprising of 8 colorectal cancer and 3 uveal melanoma patients and all with isolated liver metastases, were treated with a one hour IHP with escalating doses of oxaliplatin combined with 100 mg melphalan. Samples of blood and perfusate were taken during IHP treatment for pharmacokinetic analysis of both drugs and patients were monitored for toxicity, response and survival.
  
  
  RESULTS
  Dose limiting sinusoidal obstruction syndrome (SOS) occurred at 150 mg oxaliplatin. The areas under the concentration-time curves (AUC) of oxaliplatin at the maximal tolerated dose (MTD) of 100 mg oxaliplatin ranged from 11.9 mg/L h to 16.5 mg/L h. All 4 patients treated at the MTD showed progressive disease 3 months after IHP.
  
  
  CONCLUSIONS
  In view of similar and even higher doses of oxaliplatin applied in both systemic treatment and hepatic artery infusion (HAI), applying this dose in IHP is not expected to improve treatment results in patients with isolated hepatic metastases.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: L B J
authors.initials: LB
authors.lastname: van Iersel
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: de Leede
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: A L
authors.initials: AL
authors.lastname: Vahrmeijer
authors.affiliation: Department of Extra Corporal Circulation, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: F G J
authors.initials: FG
authors.lastname: Tijl
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: den Hartigh
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: P J K
authors.initials: PJ
authors.lastname: Kuppen
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: H H
authors.initials: HH
authors.lastname: Hartgrink
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: J W R
authors.initials: JW
authors.lastname: Nortier
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: R A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Electronic address: c.j.h.van_de_velde@lumc.nl.
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D020714:Maximum Tolerated Dose; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011446:Prospective Studies; D016896:Treatment Outcome; D014604:Uveal Neoplasms / Q000473:pathology*
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D008558:Melphalan
keywords: Colorectal cancer; Isolated hepatic perfusion; Liver metastases; Melphalan; Oxaliplatin; Uveal melanoma