The aim of this paper is to summarize data showing the role of pegylated liposomal doxorubicin (PLD) in the management of epithelial selleck screening library ovarian cancer. 2. Pegylated Liposomal Doxorubicin (PLD): Development, Structure and Pharmacokinetic Features Anthracyclines have been for years among the drugs administered for the majority of gynecologic cancers. Before taxanes were introduced into first-line therapy of ovarian cancer, anthracyclines
demonstrated a comparable Inhibitors,research,lifescience,medical efficacy, in monochemotherapy, with alkylating agents and superiority of the combination of both when compared to single-agent therapy. Furthermore, meta-analysis data suggest that the addition of anthracyclines to cisplatin might be advantageous compared to using cisplatin alone [9, 10]. Attempts have been made to introduce anthracyclines in combination with carboplatin-paclitaxel. In the randomized trial, conducted by the AGO group in collaboration with the French group GINECO, the addition of epirubicin (TEC arm) to the platinum/paclitaxel Inhibitors,research,lifescience,medical (TC arm) combination in first-line ovarian cancer treatment patients showed a not statistically significant advantage of about 5 months in median overall survival time (45.8 versus 41.0 months, HR 0.93) [11], with no progression-free survival benefit
Inhibitors,research,lifescience,medical (18.4 versus 17.9 months, HR 0.95) at the Inhibitors,research,lifescience,medical price of a greater toxicity of TEC versus TC arm (grade 3/4 hematologic, nausea/emesis, mucositis, and infections). Despite the antitumor activity in ovarian cancer, the clinical use of conventional anthracyclines is limited by their associated side effects. The haematological toxicity and the cumulative and irreversible cardiac damage (congestive heart failure) are the more common side effects, dose limiting, of anthracyclines. As far as it is elucidated, cardiotoxic events take place by increasing oxidative stress, suppression of gene expression, and induction Inhibitors,research,lifescience,medical of apoptosis on cardiac tissue [12] with clinical manifestations reaching from acute cardiac heart failure to chronic cardiac insufficiency. Several
treatment Drug_discovery strategies, including the development of new formulations for delivering the cytotoxic agents (as liposomes encapsulation), have been proposed to improve the therapeutic index of anthracyclines [13]. The inclusion of anthracyclines in a liposomal structure has been proposed to reduce side effects and to enhance the antitumor activity. In this paper, we will focus on the pharmacologic properties of pegylated liposomal doxorubicin (PLD), a new available formulation of doxorubicin that is encapsulated in a pegylated liposome [14, 15]. The size of the liposomes, approximately 100nm, prevents them from U0126 MEK entering tissues with tight capillary junctions, such as the heart and gastrointestinal tract [16].
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