Scotte, F., Banu, E., Medioni, J., Levy, E., Ebenezer, C., Marsan, S., . . . Oudard, S. (2008). Matched case-control phase 2 study to evaluate the use of a frozen sock to prevent docetaxel-induced onycholysis and cutaneous toxicity of the foot. Cancer, 112, 1625–1631. 

To assess the efficacy and safety of cold therapy in the prevention of docetaxel-induced onycholysis and skin toxicity of the foot

Patients wore an Elasto-Gel (Akromed, France) flexible frozen sock (FS) containing glycerin, which has thermal properties that allow its use in cold or hot therapies. The FS covered participants' right foot up to the ankle. The FS was refrigerated for at least three hours at –250 C to –300 C. The FS was worn at each docetaxel infusion for a total of 90 minutes (from 15 minutes before administration to 15 minutes postdocetaxel hourly infusion). Two FSs were used successively (45 minutes each) to maintain coolness. The left foot was not protected and acted as the control.

• N = 48   
• MEDIAN AGE = 62 years (range = 36–80 years)
• MALES: 36 (75%), FEMALES: 12 (25%)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Variety of tumor types; undergoing docetaxel at 70–100mg /m² every three weeks for one-hour infusions, alone or in combination therapy
• OTHER KEY SAMPLE CHARACTERISTICS: No prior taxane therapies, absence of skin and nail disorders, life expectancy of at least three months and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. All patients provided written informed consent.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: French center

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care

Prospective, convenience, case-controlled, phase II study of 50 consecutive patients (unblinded)

• Two-sample Wilcoxon matched-pairs rank test adjusted for tied values to determined statistical difference
• Kaplan–Meier and log-rank methods were used to estimate and compare differences in time to toxicity occurrence.
• Common Terminology Criteria for Adverse Events (CTCAE), version 3, for onycholysis and skin toxicity
• Four-point satisfaction scale for patient comfort

The FSs led to a significant reduction in nail toxicity with 0% versus 21% (p = 0.002). Overall skin toxicity existed in 2% of FS-protected feet but only 6% of others, which was insignificant (p = 0.18). Time until nail toxicity occurrence for an unprotected foot was associated with the number of cycles (HR of 0.36, 95% confidence interval [0.17, 0.77], p = 0.008). Fifty-eight percent were satisfied and even very satisfied (19%) with the FS protection. Only 2% of patients were dissatisfied because of FS-related cold intolerance.

Cold therapy using FSs significantly reduced the incidence of docetaxel-induced foot nail toxicity, as previously demonstrated on hands using frozen gloves.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (sample characteristics)
• Findings not generalizable
• Convenience sample of consecutive patients

Greater than half (58%) the patients were satisfied with wearing the FS, with 19% being very satisfied. This would assist nursing education for the intervention. This intervention is easy to apply with no major side effects. Because the use of FSs did not significantly affect skin toxicity, a study using a type of FS that only covers toes and nails should be tested. This intervention should also be tested with patients receiving other chemotherapy agents associated with nail and skin toxicities.