Researchers from Japan may have found a way to reduce neuropathy.
Peripheral neuropathy can occur in approximately three-quarters of patients undergoing treatment with paclitaxel chemotherapy and can persist for a full year in up to 80 percent of those patients. Further, chemotherapy-induced peripheral neuropathy (CIPN) can cause dose delays, dose reductions or treatment discontinuation in nearly 25 percent of patients.
“Paclitaxel is a key drug for breast cancer management. It is the standard chemotherapy for adjuvant and also the metastatic setting,” said Hiroshi Ishiguro in an interview with CURE. “However, there is also a significant toxicity — peripheral neuropathy — which is very common, and when it occurs, it lasts for many years sometimes.”
Though there are currently no proven treatments or ways to prevent this potentially debilitating side effect, Ishiguro and his colleagues from Kyoto University in Japan may have found a way to provide relief.
With the addition of frozen gloves and socks during treatment, objectively assessed CIPN was reduced from 81 to 28 percent in the hands and 64 to 25 percent in the feet of patients with breast cancer. Results from this study of 36 individuals were presented in a poster session during the 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO), a gathering of 30,000 oncology professionals in Chicago.
The gloves and socks are stored inside a freezer set at -22 degrees Fahrenheit for more than three hours, typically overnight. A previous study by Ishiguro, though, showed that degree of freezing does not alter the efficacy of the gloves in preventing chemotherapy-induced nail toxicity in patients with breast cancer.
On the poster, the study’s authors stated that they were confident about the efficacy of the gloves and socks.
“This easy and safe strategy will be clinically applicable and improve the quality of life of cancer patients undergoing chemotherapy,” they wrote.
Ishiguro said the gloves and socks cost about $80 each — he gets them at a discounted price — and that each patient uses four gloves and four socks. Though this adds up to $640 per patient, Ishiguro pointed out that the gloves and socks are reusable and called the method “very cost-effective.”
Patients were included on the study if they were treated with weekly paclitaxel chemotherapy for at least 12 cycles. Gloves and socks were worn for 15 minutes during the pre-medication time, for the entirety of the 60 minutes of chemotherapy infusion and then for 15 minutes during post-medication (totaling 90 minutes). Frozen gloves and socks were replaced halfway through chemotherapy infusion.
One aspect of the trial was unique: Each of the 36 patients wore a frozen glove and sock on their dominant hand and foot, and their non-dominant side acted as the control. Researchers noted that no patients dropped out because of cold intolerance.
The research team was primarily interested in objective incidence of any-grade CIPN as assessed by the Semmes—Weinstein monofilament test, but also evaluated patient-reported symptoms using a questionnaire. Further, researchers were interested in monitoring changes to small nerves using thermal threshold testing and “manipulative dexterity” using the “grooved pegboard test.” Patients were evaluated before each of the 12 cycles of chemotherapy.
The incidence of objectively assessed CIPN was significantly reduced from 81 to 28 percent in hands and 64 to 25 percent in feet. Incidence of patient-reported CIPN symptoms was also lower in hands (58 percent at baseline versus 8 percent) and feet (67 percent versus 19 percent). Further, thermal threshold to hot was reduced significantly in both hands and feet, and though a reduction in thermal threshold to cold was also observed, the data were not statistically significant.
In addition to the small study size, Ishiguro said limitations of the study were lack of blinding and randomization. Further, patients were not followed long-term after chemotherapy.
Despite these limitations, Ishiguro said he believes frozen gloves and socks are ready for standard use.
“[Frozen gloves and socks improve] patient quality of life, because they have almost no clinically significant neuropathy, so I think it should be done in all patients,” Ishiguro said.
On their poster, Ishiguro and colleagues reviewed other methods of cryotherapy that have been previously studied and shown benefit: ice chips in the mouth to reduce fluorouracil-induced mucositis, scalp cooling to reduce hair loss caused by chemotherapy and cold packs over the eyes to reduce 5-FU-induced ocular toxicity.
Notably, the DigniCap cooling cap system received FDA clearance in December 2015 for marketing in the U.S. for use in breast cancer patients who are receiving chemotherapy.
One concern with the DigniCap system was that the cooled scalp would not absorb chemotherapy and would be susceptible to metastases. When asked if chemotherapy absorption was a concern with the frozen gloves and socks, Ishiguro said metastasis in hands and feet is extremely rare and that he has not seen it occur in his practice.
Additional questions do remain, according to Ishiguro.
“The only thing we couldn’t find out is who will get the neuropathy” despite using the frozen socks and gloves, Ishiguro said. “We don’t have data yet — [that] may be an area of future research.”