Bleomycin pharmacokinetics of bolus bleomycin dose in elderly cancer patients treated with electrochemotherapy
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With the aim to determine effective therapeutic window of electrochemotherapy, we analyzed bleomycin pharmacokinetic parameters in elderly patients.
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.
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.
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.
KeywordsElectrochemotherapy Elderly patients Bleomycin Pharmacokinetics Head and neck tumors Skin metastases
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.
- 7.Buxton IO, Benet LZ (2011) Pharmacokinetics: the dynamics of drug absorption, distribution, metabolism, and elimination. In: Brunton LL, Chabner BA, Knollmann BC (eds) Goodman & Gilman’s the pharmacological basis of therapeutics, 12th edn. McGraw-Hill, New YorkGoogle Scholar
- 13.Testori A, Tosti G, Martinoli C, Spadola G, Cataldo F, Verrecchia F, Baldini F, Mosconi M, Soteldo J, Tedeschi I, Passoni C, Pari C, Di Pietro A, Ferrucci PF (2010) Electrochemotherapy for cutaneous and subcutaneous tumor lesions: a novel therapeutic approach. Dermatol Ther 23:651–661. doi: 10.1111/j.1529-8019.2010.01370.x CrossRefPubMedGoogle Scholar
- 17.Mir LM, Gehl J, Sersa G, Collins CG, Garbaya JR, Billarda V, Geertsend PF, Rudolf Z, O’Sullivanf GC, Marty M (2006) Standard operating procedures of the electrochemotherapy: instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the CliniporatorTM by means of invasive or non-invasive electrodes. EJC Supp 4:14–25CrossRefGoogle Scholar
- 18.Eisenhauera EA, Therasseb P, Bogaertsc J, Schwartzd LH, Sargente D, Fordf R, Danceyg J, Arbuckh Gwytheri S, Mooneyg M, Rubinsteing L, Shankarg L, Doddg L, Kaplanj R, Lacombec D, Verweijk J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. doi: 10.1016/j.ejca.2008.10.026 CrossRefGoogle Scholar
- 19.Groselj A, Kos B, Cemazar M, Urbancic J, Kragelj G, Bosnjak M, Veberic B, Strojan P, Miklavcic D, Sersa G (2015) Coupling treatment planning with navigation system: a new technological approach in treatment of head and neck tumors by electrochemotherapy. Biomed Eng Online 14(Suppl 3):S2. doi: 10.1186/1475-925X-14-S3-S2 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Kenakin TP (ed) (2014) Tecniques for more effective and strategic drug discovery. In: A pharmacology primer, 4 edn. Academic Press, San Diego, pp 213–253Google Scholar
- 29.Edhemovic I, Brecelj E, Gasljevic G, Marolt Music M, Gorjup V, Mali B, Jarm T, Kos B, Pavliha D, Grcar Kuzmanov B, Cemazar M, Snoj M, Miklavcic D, Gadzijev EM, Sersa G (2014) Intraoperative electrochemotherapy of colorectal liver metastases. J Surg Oncol 110:320–327. doi: 10.1002/jso.23625 CrossRefPubMedGoogle Scholar
- 30.Solari N, Spagnolo F, Ponte E, Quaglia A, Lillini R, Battista M, Queirolo P, Cafiero F (2014) Electrochemotherapy for the management of cutaneous and subcutaneous metastasis: a series of 39 patients treated with palliative intent. J Surg Oncol 109:270–274. doi: 10.1002/jso.23481 CrossRefPubMedGoogle Scholar