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The use of cryotherapy can help prevent chemotherapy-induced peripheral neuropathy (CIPN) in cancer patients, Japanese investigators have found.

Specifically, researchers found that having breast cancer patients wear frozen gloves and socks for 90 minutes after undergoing treatment with paclitaxel helped control symptoms of neuropathy that are otherwise a common side effect of cancer treatments.

The researchers, led by , MS, of Kyoto University, reported their findings in the .

CIPN is a frequent, disabling side effect of cancer treatments -- particularly taxane and platinum therapies, Hanai and colleagues explained. In fact, a recent study published in the Journal of Clinical Oncology reported that almost half of women cancer survivors suffer from persistent CIPN for many years after their treatment ended.

Duloxetine (Cymbalta) has been recommended for CIPN, but it has limited efficacy for chemotherapy-induced pain, and none for numbness or functional disability. Furthermore, Hanai and her colleagues pointed out, "no established strategy exists for CIPN prevention."

In this study, breast cancer patients were treated weekly with the taxane paclitaxel (80 mg/m2 for one hour) and then wore frozen gloves and socks on their dominant sides for 90 minutes, which included the duration of the chemotherapy treatment. Symptoms on the treated side were then compared to symptoms on the untreated (control) side.

The primary endpoint assessment was the incidence of CIPN (defined as a decrease in tactile sensation compared to baseline), as assessed by the Semmes-Weinsten monofilament test at a cumulative dose of 960 mg/m².

The researchers also assessed patients' abilities to perceive thermosensory disturbances and vibrations, as well as their manipulative dexterity. Patients' subjective symptoms were also assessed using the Japanese version of the Patient Neuropathy Questionnaire (PNQ).

Of the 40 patients in the study, 36 reached the cumulative dose. Four dropped out due to severe liver dysfunction, macular edema, severe fatigue, and a recurrence of pneumonia), but no patient dropped out because they couldn't tolerate exposure to the cold gloves and socks.

Hanai and her colleagues found that the incidence of both objective and subjective CIPN symptoms was significantly lower -- both clinical and statistically -- for the intervention side than the control side. For hand tactile sensitivity, rates were 27.8% versus 80.6%, and for foot tactile sensitivity they were 25.0% versus 63.9% (P<0.001 for both).

The percentage of patients who experienced a reduced perception of warmth was also clinically and statistically significantly lower for the intervention side (hand, 8.8% versus 32.4%; foot, 33.4% versus 57.6%, P<0.05 for both).

The manipulative dexterity assessment using a grooved pegboard test found that the control group had a greater delay in performing the task compared to baseline (-2.5 second delay on the intervention side, compared to a +8.6-second delay on the control side; P=0.005).

PNQ scores were significantly lower on the intervention side as well.

Study limitations included the fact that "placebo effects" were inevitable in the study, the non-dominant hand and foot always served as the control (as was the case in previous cryotherapy studies), and that the researchers didn't follow the subjects after completion of chemotherapy because post-treatment therapies could impact the patients' sensory status.

"We conclude that cryotherapy is a simple, safe, and effective strategy for the prevention of CIPN in patients with cancer undergoing paclitaxel treatment," Hanai and colleagues concluded. "Cryotherapy could support the delivery of optimal chemotherapy by preventing a dose delay or reduction, as well as inhibiting the deterioration of quality of life in cancer patients during and after treatment."

In an editorial accompanying the study, Dawn L. Hershman, MD, of the Herbert Irving Comprehensive Cancer Center at Columbia University in New York City, said that despite the success of this trial, it remains unclear whether cryotherapy would benefit patients undergoing platinum therapy.

If the current results are confirmed, however, cryotherapy should prove superior to agents that are customarily used to treat CIPN, such as duloxetine, Hershman wrote. "[C]ryotherapy has the advantage of a limited side effect profile, it is low cost, and appears to prevent components of CIPN other than neuropathic pain."

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