The effectiveness of regional cooling for paclitaxel-induced peripheral neuropathy

Abstract

Background: There are currently no promising therapies available to treat or prevent peripheral neuropathy (PN) induced by anticancer drugs in a cumulative dose-dependent manner. In this study, we investigated the efficacy of regional cooling of hands and feet in preventing paclitaxel (PTX)-induced PN.

Methods: Patients with gynecologic cancer who received a tri-weekly cycle of chemotherapy including PTX at doses of 150-175 mg/m² were included in this study. Regional cooling was performed by covering patient hands and feet with cold insulators during PTX administration (regional cooling group). The primary end-point was ≥grade 2 PN evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. The secondary end-points were the frequency of PN therapeutic drug use, PTX dose reduction due to PN, and adverse events due to regional cooling. The efficacy of regional cooling was compared with data retrospectively extracted from the medical records of patients who did not receive regional cooling (control group). All end-points were evaluated for up to six cycles.

Results: There were 40 and 142 patients in the regional cooling and control groups, respectively. As a primary end-point, incidences of ≥grade 2 PN in the fourth to sixth cycles were significantly lower than that in the cooling group (5.0-9.1 % vs. 19.8-31.6 %, p < 0.05 after the fourth cycle and p < 0.01 after the fifth cycle). Among secondary end-points, neither the use of PN therapeutic drugs nor the PTX dose reduction due to PN were significantly lower in the cooling group than in the control group (27.5 vs. 36.6 %, p = 0.378 and 5.0 vs. 3.5 %, p = 0.645, respectively). There were no serious regional cooling-associated adverse events such as frostbite.

Conclusions: Regional cooling of hands and feet during PTX administration might have good effectiveness and tolerability, suggesting this approach as a potentially effective supportive care to prevent PTX-induced PN.

Trial registration: The trial approval number in the institution; H25-26. Registered 5 June 2014.

Keywords: Chemotherapy; Gynecologic cancer; Paclitaxel; Peripheral neuropathy; Regional cooling.

Fig. 1

Cold insulators for hands (a) and feet (b). Figure 1 indicated cold insulators used in this study. The pre-cooled insulators were fitted on both hands and feet. The insulators were changed hourly

Fig. 2

Consort diagram in this study. Figure 2 indicated the consort diagram of this study. Sixty three patients agreed to the participation in the study and received regional cooling. Forty patients who were able to continue chemotherapy were analyzed. As the control group, 225 patients who received similar chemotherapy in the period before intervention of the regional cooling were retrospectively extracted from medical chart. One hundred-forty two patients were analyzed

Fig. 3

Effect of the regional cooling on the incidence of Grade ≥2 PN. Figure 3 indicated the incidence of Grade ≥2 PN. The black bar indicated the PN incidence of control group (n = 142) in each cycle. The white bar indicated the PN incidence of regional cooling group (n = 40) in each cycle. The comparison of the both groups in each cycle performed by a chi-square test