Frozen Gloves, Socks Reduce CIPN in Patients With Breast Cancer

Pam Harrison

October 12, 2017

Getting patients with breast cancer to wear frozen gloves and socks for 90 minutes while receiving weekly paclitaxel chemotherapy significantly reduces objective and subjective assessments of chemotherapy-induced peripheral neuropathy (CIPN) across at least 12 treatment cycles, a self-controlled, prospective study indicates.

"CIPN is a substantial clinical problem, there is no good prevention of it except to not give the drug or to decrease the dose, and there's limited benefit for treating established neuropathy," Charles Loprinzi, MD, professor of breast cancer research, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News. He was not involved in this research and was approached for comment.

"So this study is clearly interesting and the data do support the fact that cryotherapy seems to work, but it would be nice to have more data before we can really recommend it," he added.

The study was published online October 12 in the Journal of the National Cancer Institute.

Coauthor Hiroshi Ishiguro, MD, PhD, Kyoto University, Japan, and colleagues report that 44 patients were enrolled in the trial, 36 of whom were evaluable for the analysis at study endpoint.

"Each patient wore frozen flexible gloves and socks [Elasto-Gel, Akromed] on the dominant hand and foot from 15 minutes before paclitaxel administration to 15 minutes after the infusion was complete," the investigators write. "The nondominant side acted as the untreated control," they add.

Participants were given another pair of frozen gloves, though not socks, 45 minutes after the intervention had been initiated.  

Patients were assessed for symptoms of CIPN at multiple time points: at baseline and before they received each cycle of chemotherapy during outpatient care. Chemotherapy consisted of weekly paclitaxel at a dose of 80 mg/m2.

Symptoms of CIPN were also assessed when patients had reached a cumulative treatment dose of 960 mg/m2 — the dose recommended for both neoadjuvant and adjuvant weekly paclitaxel therapy.

Twenty-five of the 36 evaluable participants reached the cumulative dose of 960 mg/m2, while another 11 patients received even higher doses, the researchers point out. 

"The primary end point was the incidence of CIPN (any grade), defined as a decline in tactile sensation from the pretreatment baseline as assessed by the Semmes-Weinstein monofilament test," study authors note. This test is the most widely used test to diagnose the loss of protective sensation, one component of CIPN.  

On the dominant side, where patients had been treated with cryotherapy, 27.8% of hands had detectable tactile deterioration — the definition of CIPN for the study — compared with 80.6% of untreated hands (P < .001).


Similarly, 25% of feet that had been treated with cryotherapy had evidence of tactile deterioration at study endpoint compared with 63.9% of untreated feet (P < .001).

Large differences between treated and untreated hands and feet were also detected in several secondary endpoints.

For example, perception of warmth was reduced in only 8.8% of treated hands vs 32.4% of untreated hands (P = .02) and in 33.4% of treated feet vs 57.6% of untreated feet (P = .04).

Compared with baseline, delay in performance speed (also referred to as delay in manipulate dexterity) was greater on the untreated side at 8.6 seconds compared with a –2.5-second delay on the intervention side (P = .005).

At a cumulative dose of 960 mg/m2, sensory dysfunction was almost prevented, with only 2.8% of treated hands developing symptoms of severe CIPN as assessed by the Patient Neuropathy Questionnaire (PNQ) compared with 41.7% of untreated hands (P < .001).

For severe CIPN of the foot, percentages were nearly identical, with only 2.8% of treated feet developing severe CIPN compared with 36.1% of untreated feet, again based on PNQ assessment.

"CIPN also occurred faster on the control side than on the intervention side," the investigators observe (P < .001). "Furthermore, no patients dropped out due to cold intolerance."

The few adverse events resulting from cryotherapy resolved almost immediately.

"Compression therapy [using surgical gloves] and cryotherapy share an analogous mechanism of reduced drug exposure due to vasoconstriction during paclitaxel infusion," the investigators explain.

"We conclude that cryotherapy is a simple, safe, and effective strategy for the prevention of CIPN in patients with cancer undergoing paclitaxel treatment," they suggest.

Accompanying Editorial

In an accompanying editorial, Dawn Hershman, MD, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York City, cautions that the pathophysiology of CIPN may vary depending on the chemotoxic agent used, and it is not clear whether cryotherapy can prevent CIPN induced by a drug such as oxaliplatin, which also causes a lot of CIPN. 

"If the results are confirmed, cryotherapy has the advantage of a limited side effect profile, it is low cost, and it appears to prevent components of CIPN other than neuropathic pain," Dr Hershman writes.

Further Study

Commenting further on cryotherapy for the prevention of CIPN, Dr Loprinzi said that there is in fact a larger study, with accrual completed, in which where  investigators, including Dr Loprinzi, will be evaluating topical cryotherapy for reducing pain in patients with CIPN or the paclitaxel-induced acute pain syndrome (the ACCRU trial).

He also pointed out that further support for the benefit of using surgical gloves to protect patients against paclitaxel-induced CIPN was published last year at the American Society of Clinical Oncology (ASCO) annual meeting, where investigators reported significant reductions in both sensory and motor neuropathy in hands protected by a surgical glove during chemotherapy compared with unprotected hands.

"Our trial should be reported at ASCO 2018, and hopefully we will see enough information about cryotherapy in CIPN by then that will allow us to proceed with it," Dr Loprinzi said.

The study was funded by the Japan Society for the Promotion of Science and the Promotion Plana for the Platform of Human Resource Development for Cancer. The study authors and Dr Hershman have disclosed no relevant financial relationships. Dr Loprinzi has received personal fees from Cubist Pharmaceuticals, Coronado Biosciences, Mitsubishi Tanabe Pharma, PledPharma, Lpath, and Mundipharma for consultations not directly related to the current article.

J Natl Cancer Inst. Published online October 12, 2017. Abstract, Editorial

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