Hanai, A., Ishiguro, H., Sozu, T., Tsuda, M., Yano, I., Nakagawa, T., . . . Tsuboyama, T. (2018). Effects of cryotherapy on objective and subjective symptoms of paclitaxel-induced neuropathy: Prospective self-controlled trial. Journal of the National Cancer Institute, 110, 141–148.

To investigate the effectiveness of cryotherapy to prevent paclitaxel-induced peripheral neuropathy.

Each patient wore frozen flexible gloves and socks on their dominant hand and foot (15 minutes before paclitaxel administration to 15 minutes after the infusion was complete: 90 minutes total). Gloves were replaced after the first 45 minutes.

• N = 36   
• AGE: Mean age = 56 years, SD = 13.8
• MALES (%): Not reported  
• FEMALES (%): Not reported
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer undergoing paclitaxel therapy
• OTHER KEY SAMPLE CHARACTERISTICS: Body mass index (BMI) mean score = 22.4

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Kyoto University Hospital, Japan

PHASE OF CARE: Active antitumor treatment

Controlled clinical trial where patients served as their own controls

Symptoms were assessed before chemotherapy at baseline and before each subsequent cycle. Semmes-Weinstein monofilament test (PN, tactile disturbance), thermal simulator to measure thermosensory disturbance (objective symptoms), tuning form to measure vibration perception (objective symptoms), manipulative dexterity to measure performance speed (objective symptom), PROs (Japanese version of the PNQ a validated measure of neuropathy and activities of daily living), cryotherapy tolerability (ad hoc questions), electrophysiological signs (conduction velocity and action potential amplitude of the median nerve), and PKs36

No patients dropped out due to cold intolerance. Pain was reported in 8.2%, and feeling cold was reported in 4.2%. The primary endpoint was tactile deterioration, which was clinically and statistically significantly lower for the intervention side (hand = 27.8% versus 80.6%, OR = 20, p < 0.001; foot = 25% versus 63.9%, OR = infinite, p < 0.001). For secondary endpoints, CIPN occurred faster on the control side than on the intervention side (hand HR = 0.13; foot HR = 0.13). Additional secondary endpoints also reported.

Cryotherapy appears to have efficacy for the prevention of CIPN. In this study, the development of subjective CIPN symptoms was almost completely prevented at a cumulative dose of 960 mg/m².

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: No information on gender or smoking history. No information was provided about the manufacturer of the gloves or socks and the cost. Unknown cost and workflow implications for patients and staff/institution.

Cryotherapy is a promising intervention to prevent CIPN. Additional studies are needed to determine the long-term effects of this therapy on the development of CIPN symptoms in patients treated with paclitaxel.