Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia: a literature review of pharmaceutical and clinical aspects

Objectives

The rate of dermal toxicity has been shown to increase in patients receiving pegylated liposomal doxorubicin (PLD), particularly palmar-plantar erythrodysesthesia (PPE). However, it is difficult to diagnose and treat PLD-related PPE due to its delayed dermal performance, unclear pathogenetic mechanism, and the lack of specific preventive measures. The aim of this study was to provide potential management strategies for PPE associated with PLD.


Methods

The current article reviews the available data regarding the pharmacological and clinical aspects of PLD, including the formulation and pharmacokinetics of PLD, dose and schedule contribution to PPE, concomitant drugs affecting skin toxicity of PLD, the pathogenesis of PPE, and preventive measures and treatment of PLD-related PPE.


Results

The long circulation structure of polyethylene glycol liposomes may be one of the reasons for PPE. PLD has radically different pharmacokinetic characteristics, including prolonged blood circulation time, decreased body distribution volume, and slow clearance. Altering the schedules and doses of PLD or combining it with platinum compounds can optimise clinical efficacy and minimise the occurrence of PPE. Doses of 150–200 mg of pyridoxine daily have been widely used for the prevention and treatment of PPE. Regional cooling and plasma filtration have been used for PPE prophylaxis.


Conclusions

To date, the mechanism of PPE induced by PLD remains unclear, and no complete preventive medication has been established. Further research and prospective randomised studies are needed to understand the management options in PLD-related PPE.