L B J van Iersel1, E M de Leede2, A L Vahrmeijer2, F G J Tijl3, J den Hartigh4, P J K Kuppen2, H H Hartgrink2, H Gelderblom1, J W R Nortier1, R A E M Tollenaar2, C J H van de Velde5. 1. Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. 2. Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. 3. Department of Extra Corporal Circulation, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. 4. Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. 5. Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands. Electronic address: c.j.h.van_de_velde@lumc.nl.
Abstract
AIM: 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.
AIM: 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 melanomapatients 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: Eleonora M de Leede; Mark C Burgmans; Christian H Martini; Fred G J Tijl; Arian R van Erkel; Jaap Vuyk; Ellen Kapiteijn; Cornelis Verhoef; Cornelis J H van de Velde; Alexander L Vahrmeijer Journal: J Vis Exp Date: 2016-07-31 Impact factor: 1.355
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