Plasmafiltration as an effective method in the removal of circulating pegylated liposomal doxorubicin (PLD) and the reduction of mucocutaneous toxicity during the treatment of advanced platinum-resistant ovarian cancer

• Published in: Cancer chemotherapy and pharmacology Vol. 85; no. 2; pp. 353 - 365
• Main Authors: Kubeček, Ondřej, Martínková, Jiřina, Chládek, Jaroslav, Bláha, Milan, Maláková, Jana, Hodek, Miroslav, Špaček, Jiří, Filip, Stanislav
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2020; Springer Nature B.V
• Subjects: Adult; Aged; Antibiotics, Antineoplastic - adverse effects; Anticancer properties; Apheresis; Cancer Research; Chemotherapy; Doxorubicin; Doxorubicin - adverse effects; Doxorubicin - analogs & derivatives; Drug-Related Side Effects and Adverse Reactions - drug therapy; Exposure; Female; High performance liquid chromatography; Historical account; Humans; Liquid chromatography; Medicine; Medicine & Public Health; Middle Aged; Mucositis; Oncology; Organoplatinum Compounds - therapeutic use; Original Article; Ovarian cancer; Ovarian Neoplasms - drug therapy; Pharmacokinetics; Pharmacology/Toxicology; Platinum; Polyethylene Glycols - adverse effects; Prospective Studies; Side effects; Survival; Toxicity; Population kinetics; Pegylated liposomal doxorubicin (PLD); Cancer therapy; EPR effect; Mucocutaneous toxicity; Ovarian cancer; Hand–foot syndrome; Plasmapheresis
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-019-03976-2

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/m
2
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.