PURPOSE: The present study evaluates the safety and efficacy of double-plasma filtration (PF) to remove the exceeding pegylated liposomal doxorubicin (PLD) in circulation, thus reducing mucocutaneous toxicity. METHODS: A total of 16 patients with platinum-resistant ovarian cancer were treated with 50 mg/m2 PLD applied in 1-h IV infusion every 28 days. PF was scheduled at 44-46 h post-infusion. The concentration of plasma PLD and non-liposomal doxorubicin (NLD) was monitored with high-performance liquid chromatography at 116 h post-infusion. A non-linear method for mixed-effects was used in the population pharmacokinetic model. The dose fraction of PLD eliminated by the patient prior to PF was compared with the fraction removed by PF. PLD-related toxicity was recorded according to CTCAE v4.0 criteria and compared to historical data. Anticancer effects were evaluated according to RECIST 1.1 criteria. RESULTS: The patients received a median of 3 (2-6) chemotherapy cycles. A total of 53 cycles with PF were evaluated, which removed 31% (10) of the dose; on the other hand, the fraction eliminated prior to PF was of 34% (7). Exposure to NLD reached only 10% of exposure to the parent PLD. PLD-related toxicity was low, finding only one case of grade 3 hand-foot syndrome (6.7%) and grade 1 mucositis (6.7%). Other adverse effects were also mild (grade 1-2). PF-related adverse effects were low (7%). Median progression-free survival (PFS) and overall survival (OS) was of 3.6 (1.5-8.1) and 7.5 (1.7-26.7) months, respectively. Furthermore, 33% of the patients achieved stable disease (SD), whereas that 67% progressed. CONCLUSION: PF can be considered as safe and effective for the extracorporeal removal of PLD, resulting in a lower incidence of mucocutaneous toxicity.

4th Department of Internal Medicine Hematology Faculty of Medicine University Hospital in Hradec Králové Charles University Sokolská 581 50005 Hradec Králové Czech Republic

Department of Obstetrics and Gynecology Faculty of Medicine University Hospital in Hradec Králové Charles University Sokolská 581 50005 Hradec Králové Czech Republic

Department of Oncology and Radiotherapy Faculty of Medicine University Hospital in Hradec Králové Charles University Sokolská 581 50005 Hradec Králové Czech Republic

Department of Pharmacology Faculty of Medicine in Hradec Králové Charles University Šimkova 870 50003 Hradec Králové Czech Republic

Department of Surgery Faculty of Medicine University Hospital in Hradec Králové Charles University Sokolská 581 50005 Hradec Králové Czech Republic

Institute of Clinical Biochemistry and Diagnostics Faculty of Medicine University Hospital in Hradec Králové Charles University Sokolská 581 50005 Hradec Králové Czech Republic

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Therapeutic Apheresis, Circulating PLD, and Mucocutaneous Toxicity: Our Clinical Experience through Four Years