title: Extracorporeal Elimination of Circulating Pegylated Liposomal Doxorubicin (PLD) to Enhance the Benefit of Cytostatic Therapy in Platinum-Resistant Ovarian Cancer Patients.
abstract: Ovarian cancer is the fifth most common malignancy in the world's female population and with the highest lethality index among gynecological tumors. The prognosis of metastatic disease is usually poor, especially in platinum-resistant cases. There are several options for the treatment of metastatic disease resistant to platinum derivates (e.g. paclitaxel, topotecan and pegylated liposomal doxorubicin), all of which are considered equipotent. Pegylated liposomal doxorubicin (PLD) is a liposomal form of the anthracycline antibiotic doxorubicin. It is characterized by more convenient pharmacokinetics and a different toxicity profile. Cardiotoxicity, the major adverse effect of conventional doxorubicin, is reduced in PLD as well as hematotoxicity, alopecia, nausea and vomiting. Skin toxicity and mucositis, however, emerge as serious issues since they represent dose and schedule-limiting toxicities. The pharmacokinetics of PLD (prolonged biological half-life and preferential distribution into tumor tissue) provide new possibilities to address these toxicity issues. The extracorporeal elimination of circulating liposomes after PLD saturation in the tumor tissue represents a novel and potent strategy to diminish drug toxicity. This article intends to review PLD characteristics and the importance of extracorporeal elimination to enhance treatment tolerance and benefits.
authors.affiliation: Department of Oncology and Radiotherapy, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic. okubec@gmail.com.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Kubeček
authors.affiliation: 4th Department of Internal Medicine - Haematology, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Bláha
authors.affiliation: Department of Histology and Embryology, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic.
authors.forename: Daniel
authors.initials: D
authors.lastname: Diaz-Garcia
authors.affiliation: Department of Oncology and Radiotherapy, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Filip
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000097:blood* / Q000627:therapeutic use*; D054697:Cytostatic Agents; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005112:Extracorporeal Circulation; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy*; D017671:Platinum Compounds / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use
chemical_list: D000903:Antibiotics, Antineoplastic; D054697:Cytostatic Agents; D017671:Platinum Compounds; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Palmar-plantar erythrodysesthesia; Pegylated liposomal doxorubicin; Rheopheresis; Toxicity