Mangili, G., Petrone, M., Gentile, C., De Marzi, P., Vigano, R., & Rabaiotti, E. (2008). Prevention strategies in palmar-plantar erythrodysesthesia onset: The role of regional cooling. Gynecologic Oncology, 108, 332–335.

To evaluate the effectiveness of strategies to prevent ​palmar-plantar erythrodysesthesia (PPE) incidence, including regional cooling, behavioral rules, and lower-dose pegylated liposomal doxorubicin (PLD), in patients with gynecologic malignancies.

PLD doses ranged from 30 to 50 mg/m² every 21 to 28 days. All patients received premedication with oral dexamethasone 8 mg (12 hours before PLD) and pyridoxine 300 mg PO daily. All patients were advised to follow strict behavioral rules: keep skin well hydrated, avoid sunlight, minimize trauma to the hands and feet, avoid contact with warm water, and avoid hot foods and liquids. Patients who were enrolled from 2001 to December 2003 were in the non–regional cooling group (n = 25), whereas patients who were enrolled from January 2004 to 2006 were in the regional cooling group (n = 28). Patients received regional cooling (application of ice packs around wrists and ankles) and icicles during PLD infusion.

• The study reported on a sample of patients who received PLD as a single therapy (n = 33), PLD plus carboplatin (n = 17), or PLD plus paclitaxel (n = 3).
• All patients were women with gynecologic cancers (N = 53).

Obstetrical/Gynecological Department at San Raffaele Hospital in Milan, Italy

This was a prospective, observational, single-center, nonrandomized study.

Skin toxicity was graded according to National Cancer Institute (NCI) and Gynecologic Oncology Group (GOG) criteria.

The incidence of PPE was significantly higher in the non–regional cooling group (n = 9, 36%) compared to the regional cooling group (n = 2, 7%; p = 0.0097).

Multivariant analysis revealed the use of a regional cooling protocol and lower PLD dosage were significant factors in reducing the onset and incidence of PPE. The authors estimated the probability of developing PPE in a patient who receives 30 to 35 mg/m² of PLD and follows the regional cooling protocol is 1.42%. Conversely, a patient who does not adapt this regional cooling protocol and receives 40 to 50 mg/m² of PLD every three weeks has a 60.41% estimated probability of developing PPE.

• The sample size was small.
• This was a prospective, observational, nonrandomized study. Efficacy needs to be proven in a controlled and randomized study.
• A combination of interventions was used in this study. All patients were given oral dexamethasone and oral pyridoxine as premedication. Therefore, determining the effectiveness of the individual interventions is difficult.