Limb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study

Abstract

BackgroundPeripheral neuropathy (PN) due to paclitaxel is a common dose-limiting toxicity with no effective prevention or treatment. We hypothesize that continuous-flow limb hypothermia can reduce paclitaxel-induced PN.Patients and methodsAn internally controlled pilot trial was conducted to investigate the neuroprotective effect of continuous-flow limb hypothermia in breast cancer patients receiving weekly paclitaxel. Patients underwent limb hypothermia of one limb for a duration of 3 h with every paclitaxel infusion, with the contralateral limb used as control. PN was primarily assessed using nerve conduction studies (NCSs) before the start of chemotherapy, and after 1, 3, and 6 months. Skin temperature and tolerability to hypothermia were monitored using validated scores.ResultsTwenty patients underwent a total of 218 cycles of continuous-flow limb hypothermia at a coolant temperature of 22°C. Continuous-flow limb hypothermia achieved mean skin temperature reduction of 1.5 ± 0.7°C and was well tolerated, with no premature termination of cooling due to intolerance. Grade 3 PN occurred in 2 patients (10%), grade 2 in 2 (10%), and grade 1 in 12 (60%). Significant correlation was observed between amount of skin cooling and motor nerve amplitude preservation at 6 months (p < 0.0005). Sensory velocity and amplitude in the cooled limbs were less preserved than in the control limbs, but the difference did not attain statistical significance. One patient with a history of diabetes mellitus had significant preservation of compound muscle action potential in the cooled limb on NCS analysis.ConclusionThis study suggests that continuous limb hypothermia accompanying paclitaxel infusion may reduce paclitaxel-induced PN and have therapeutic potential in select patients and warrants further investigation. The method is safe and well tolerated.

Prevention and Management of Chemotherapy-Induced Polyneuropathy

“…The hypothermia process reduces skin temperature by 1.5 ± 0.7°C. The amount of skin cooling was significantly associated with preservation of motor nerve amplitude after 6 months ( p < 0.0005) [26]. Another study with 40 patients confirms these observations: when wearing frozen gloves and socks on the dominant side for 90 min during paclitaxel infusion, patients had diminished objective and subjective symptoms of CIPN as compared to the non-dominant, untreated side [27].…”

Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy

“…The role of continuous-flow limb cooling in decreasing the incidence of CIPN has been previously described in studies by our group [2,25]. Coolant temperature of 22°C was determined to be the lowest tolerable temperature in healthy volunteers for a duration of 3 h (corresponding to the duration of chemotherapy) [2].…”

“…Coolant temperature of 22°C was determined to be the lowest tolerable temperature in healthy volunteers for a duration of 3 h (corresponding to the duration of chemotherapy) [2]. Using these data, a trial was conducted in cancer patients undergoing adjuvant paclitaxel chemotherapy with concomitant continuous-flow cooling purely on the lower limbs [25]. To have an early initial signal of efficacy, an internal randomization was performed by administering unilateral lower limb cooling while the other was a paired-control.…”

“…Only a moderate degree of cooling was achieved, with continuous-flow cooling alone, due to tolerability issues with lower temperatures. However, cancer subjects showed mild improvement in nerve conduction in the cooled leg compared to the control [25]. After much internal research, it was discovered that the addition of pressure to cooling (cryocompression) allowed for a greater level of tolerability and degree of cooling.…”

“…Tolerability and skin temperature changes were assessed, accompanied by neurophysiological and clinical assessments of neuropathy. The results of the above-mentioned assessments in subjects who underwent cryocompression were also compared with those who underwent continuous-flow cooling during chemotherapy and controls (from our previous study [25]).…”