Clinical Medicine Insights: Therapeutics

Pegylated liposomal doxorubicin (PLD) is doxorubicin HCl encapsulated in long-circulating STEALTH® liposomes (Doxil®). PLD achieves good response rates and many patients maintain long-lasting stable disease (SD), which is one of the advantages. In addition, the clinical benefit is high in platinum-resistant disease, and PLD is thus considered to be the first option. PLD is associated with a number of adverse events, but these events are mild to moderate. PLD is safer for heavily pretreated patients than topotecan and gemcitabine due to mild bone-marrow toxicity, but that nonhematotoxity, such as PPE, stomatitis, mucositis, and other cutaneous reactions were the most common side effects attributable to PLD. Based on a review of previous studies, there are no differences in efficacy between 50 and 40 mg/m2 of PLD, therefore, a dose of 40 mg/m2 is preferable in patients with platinum-resistant disease to reduce adverse events. The 1-hour infusion schedule every 4 weeks makes PLD easy to administer. A rational approach to combine PLD with other drugs should take the slow accumulation and delayed peak of PLD in tumors into consideration. When combined with other useful agents, the lower dose of PLD (30 to 35 mg/m2) with a 3-week schedule may reduce severe PPE and stomatitis with negligible effects on the level of DI and the therapeutic efficacy.