Ales Groselj1, Mojca Krzan2, Tina Kosjek3, Masa Bosnjak4, Gregor Sersa5, Maja Cemazar6,7. 1. Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia. 2. Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, Ljubljana, Slovenia. 3. Department of Environmental Sciences, Jozef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia. 4. Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia. 5. Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia. gsersa@onko-i.si. 6. Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia. mcemazar@onko-i.si. 7. Faculty of Health Sciences, University of Primorska, Polje 42, 6310, Izola, Slovenia. mcemazar@onko-i.si.
Abstract
PURPOSE: With the aim to determine effective therapeutic window of electrochemotherapy, we analyzed bleomycin pharmacokinetic parameters in elderly patients. METHODS: In prospective clinical study in the treatment of tumors with electrochemotherapy, blood samples of patients older than 65 years were collected after the bolus intravenous injection of bleomycin (15,000 IU/m(2)). In serum samples, quantitative analysis was performed with liquid chromatography coupled to high-resolution mass spectrometry. Based on the data, the pharmacokinetic parameters of bleomycin elimination were determined. RESULTS: Pharmacokinetic analysis of the data revealed a monophasic serum clearance curve, which demonstrates slow elimination of bleomycin, being less than 500 ml/min and a half-time of 30 min. CONCLUSIONS: Slow monophasic elimination of bleomycin from serum in elderly patients implies on the longer therapeutic window, from 8 to up to 40 min or even longer post-bleomycin injection for electrochemotherapy. However, prolonged therapeutic bleomycin serum concentrations may also affect the possible adverse effects, such as lung fibrosis and extensive necrosis of tumors due to the uptake of toxic bleomycin concentrations into the tumors. This may imply on lowering of bleomycin dosage, in particular in the elderly patients.
PURPOSE: With the aim to determine effective therapeutic window of electrochemotherapy, we analyzed bleomycin pharmacokinetic parameters in elderly patients. METHODS: In prospective clinical study in the treatment of tumors with electrochemotherapy, blood samples of patients older than 65 years were collected after the bolus intravenous injection of bleomycin (15,000 IU/m(2)). In serum samples, quantitative analysis was performed with liquid chromatography coupled to high-resolution mass spectrometry. Based on the data, the pharmacokinetic parameters of bleomycin elimination were determined. RESULTS: Pharmacokinetic analysis of the data revealed a monophasic serum clearance curve, which demonstrates slow elimination of bleomycin, being less than 500 ml/min and a half-time of 30 min. CONCLUSIONS: Slow monophasic elimination of bleomycin from serum in elderly patients implies on the longer therapeutic window, from 8 to up to 40 min or even longer post-bleomycin injection for electrochemotherapy. However, prolonged therapeutic bleomycin serum concentrations may also affect the possible adverse effects, such as lung fibrosis and extensive necrosis of tumors due to the uptake of toxic bleomycin concentrations into the tumors. This may imply on lowering of bleomycin dosage, in particular in the elderly patients.
Entities:
Keywords:
Bleomycin; Elderly patients; Electrochemotherapy; Head and neck tumors; Pharmacokinetics; Skin metastases
Authors: Kristoffer Hendel; Anders C N Hansen; Liora Bik; Charlotte Bagger; Martijn B A van Doorn; Christian Janfelt; Uffe H Olesen; Merete Haedersdal; Catharina M Lerche Journal: Drug Deliv Date: 2021-12 Impact factor: 6.419
Authors: Primož Strojan; Aleš Grošelj; Gregor Serša; Christina Caroline Plaschke; Jan B Vermorken; Sandra Nuyts; Remco de Bree; Avraham Eisbruch; William M Mendenhall; Robert Smee; Alfio Ferlito Journal: Cancers (Basel) Date: 2021-03-12 Impact factor: 6.639