Adverse drug reaction profile of pegylated liposomal doxorubicin versus conventional doxorubicin: An observational study

Background : Potential life-threatening cardiac toxicities limit the lifetime dose of doxorubicin. The pegylation of the molecule protects the drug from detection by methoxypolyethylene glycol resulting increase of circulation time. Encapsulation of doxorubicin inside a pegylated liposome alters bioavailability, biodistribution and thus its biological activity significantly. We conducted an intensive monitoring of the adverse drug reactions (ADRs) profile of pegylated liposomal doxorubicin (PLD) in comparison with conventional doxorubicin in a tertiary care cancer center. Materials and Methods : ADR data were collected from 30 patients receiving PLD and 30 age-matched controls receiving conventional doxorubicin in this longitudinal observational study. Severity was graded as per US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAEs). For the evaluation of acute and chronic toxicities, we adopted the basic scale from CTCAE version 4 of the National Cancer Institute. Results : The median disease duration was greater in PLD arm. Totally, 357 ADRs were noted with PLD and 375 with conventional doxorubicin. Of these, 75 (21%, 95% confidence interval [CI] 13.69-28.33%) in the PLD group and 60 (16.26%, 95% CI: 9.74-22.78%) in the conventional doxorubicin group were of grade 3/4 severity. Common events included myelosuppression, nausea, vomiting, anorexia, stomatitis, palmer-planter erythrodysesthesia, alopecia with PLD and myelosuppression, nausea, vomiting, anorexia, stomatitis, alopecia, and cardio-toxicities with conventional doxorubicin. For hematological toxicities, there was no statistical significant difference between two arms. Furthermore, gastrointestinal toxicities (nausea, vomiting, diarrhea, anorexia and stomatitis) were same for both arms. Among the skin toxicities palmar-plantar-erythrodysesthesia grade 2 toxicity was found in 60% patients receiving liposomal doxorubicin (P = 0.046). In cardio-toxicities, left ventricular ejection dysfunction found in 60% patients of conventional doxorubicin arm (P - 0.038). Conclusions: This observational study suggests that PLD has a better tolerability with less ventricular dysfunction but increased yet manageable palmar-plantar-erythrodysesthesia. This needs confirmation through further interventional study.