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

被引:31
作者
Groselj, Ales [1 ]
Krzan, Mojca [2 ]
Kosjek, Tina [3 ]
Bosnjak, Masa [4 ]
Sersa, Gregor [4 ]
Cemazar, Maja [4 ,5 ]
机构
[1] Univ Med Ctr Ljubljana, Dept Otorhinolaryngol & Cervicofacial Surg, Zaloska 2, Ljubljana 1000, Slovenia
[2] Univ Ljubljana, Fac Med, Dept Pharmacol & Expt Toxicol, Korytkova 2, Ljubljana, Slovenia
[3] Jozef Stefan Inst, Dept Environm Sci, Jamova 39, Ljubljana 1000, Slovenia
[4] Inst Oncol Ljubljana, Dept Expt Oncol, Zaloska 2, Ljubljana 1000, Slovenia
[5] Univ Primorska, Fac Hlth Sci, Polje 42, Izola 6310, Slovenia
关键词
Electrochemotherapy; Elderly patients; Bleomycin; Pharmacokinetics; Head and neck tumors; Skin metastases; II TRIAL; TUMORS; CHEMOTHERAPY; PHARMACOLOGY; PRINCIPLES; DRUG; HEAD;
D O I
10.1007/s00280-016-3004-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:939 / 947
页数:9
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