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Cancer Chemotherapy and Pharmacology

, Volume 77, Issue 5, pp 939–947 | Cite as

Bleomycin pharmacokinetics of bolus bleomycin dose in elderly cancer patients treated with electrochemotherapy

  • Ales Groselj
  • Mojca Krzan
  • Tina Kosjek
  • Masa Bosnjak
  • Gregor Sersa
  • Maja Cemazar
Original Article

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/m2). 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.

Keywords

Electrochemotherapy Elderly patients Bleomycin Pharmacokinetics Head and neck tumors Skin metastases 

Notes

Acknowledgments

The authors acknowledge the financial support from the state budget by the Slovenian Research Agency (Program Nos. P3-0003, P1-0143, P3-0067, J3-5505, J1-6744). The research was conducted in the scope of LEA EBAM (French–Slovenian European Associated Laboratory: Pulsed Electric Fields Applications in Biology and Medicine) and is a result of networking efforts within COST TD1104 Action. We would like to thank Mira Lavric (Institute of Oncology Ljubljana, Ljubljana, Slovenia) and Biserka Veberic (Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana) for all the valuable work they contributed to this research.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology and Cervicofacial SurgeryUniversity Medical Centre LjubljanaLjubljanaSlovenia
  2. 2.Department of Pharmacology and Experimental Toxicology, Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia
  3. 3.Department of Environmental SciencesJozef Stefan InstituteLjubljanaSlovenia
  4. 4.Department of Experimental OncologyInstitute of Oncology LjubljanaLjubljanaSlovenia
  5. 5.Faculty of Health SciencesUniversity of PrimorskaIzolaSlovenia

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