INCREASING DURATION OF PEGYLATED LIPOSOMAL DOXORUBICIN INCREASES ADVERSE EVENTS 

Int J Gynecol Cancer. 2013 Jan 4. [Epub ahead of print]

Evaluation of Pegylated Liposomal Doxorubicin Dose on the Adverse Drug Event Profile and Outcomes in Treatment of Recurrent Endometrial Cancer.

Julius JM, Tanyi JL, Nogueras-Gonzalez GM, Watkins JL, Coleman RL, Wolf JK, Smith JA.

Source

*Division of Pharmacy, The University of Texas MD Anderson Cancer Center; †Department of Obstetrics and Gynecology, Baylor College of Medicine; ‡Department of Biostatistics, The University of Texas MD Anderson Cancer Center; and §Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX; ∥MD Anderson-Banner, Phoenix, AZ; and ¶Department of Obstetrics, Gynecology and Reproductive Sciences, The University of Texas Health Sciences Center, Houston, TX.

Abstract

OBJECTIVE:

This study aims to determine factors that may increase the likelihood of adverse drug events (ADEs) in patients with recurrent endometrial cancer treated with pegylated liposomal doxorubicin (PLD) as well as this agent's impact on clinical outcomes.

METHODS:

The treatment records of patients with endometrial cancer who received PLD at The University of Texas, MD Anderson Cancer Center, from 1996 to 2006 were reviewed. Patient demographics, PLD dose, ADEs, use of supportive care interventions, disease progression, and survival were extracted. Logistical regression analysis was used to identify factors that were associated with higher incidence of ADEs and that influenced survival.

RESULTS:

A total of 60 patients with recurrent endometrial cancer were identified who experienced 122 ADEs. The most commonly reported ADEs were nausea (18.9%), palmar-plantar erythrodysesthesia (PPE; 16.4%), muscle weakness (12.3%), mucositis (10.7%), and peripheral neuropathy (9.8%). Seventeen patients (28%) required a dose reduction because of ADEs. However, only 5 (8.3%) patients discontinued therapy because of toxicity. Cooling mechanisms were used in 19 patients to prevent PPE, although 9 of these patients still experienced PPE. Treatment with 6 or more cycles of PLD was associated with increased incidence of neutropenia (P = 0.045), peripheral neuropathy (P = 0.004), and PPE (P < 0.001). No differences in progression-free survival or time to progression were found between the doses of PLD; however, there was an assessable trend toward increased survival with doses of 40 mg/m.

CONCLUSIONS:

Although there was no association with dose level and ADEs, more cycles received increased the incidence of toxicities, including PPE and neuropathy. There was no association between different doses of PLD and progression-free survival or time to progression.