A longitudinal tracking and quantitative assessment of paclitaxel-induced peripheral neurotoxicity

Abstract

Abstract Background Assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) usually depends on subjective grading scales, such as the Common Terminology Criteria for Adverse Events (CTCAE). We previously validated a newly developed point-of-care nerve conduction device (POCD) for the objective and quantitative assessment of CIPN. The present study used this POCD to prospectively track the natural history of paclitaxel (PTX)-related CIPN. Methods Sural nerve amplitude potentials (SNAP, μV), a quantitative measure of axonal degeneration, and sural nerve conduction velocity (SNCV, m/s), a quantitative measure of the degree of demyelination, were evaluated using a portable, automated POCD (DPN-Check®, Neurometrix Inc., Waltham, MA, USA) in patients with breast cancer scheduled to receive 12 cycles of adjuvant or neoadjuvant weekly PTX, at baseline, after every 2 cycles of PTX (on the first day of the 3rd, 5th, 7th, 11th cycles), and within 1 month after the 12th cycle of PTX. The severity of CIPN was also evaluated according to the CTCAE, version 4.0. Results 55 patients completed 12 cycles of PTX (median age 51 years, range 32-74; adjuvant/neoadjuvant = 40/15; worst CTCAE G1/G2/G3 = 32/16/7). A total of 49 patients received dose-dense EC (epirubicin + cyclophosphamide) before PTX, and 18 patients with HER2-positive breast cancer received trastuzumab concurrently with PTX. SNAP decreased significantly during each cycle of chemotherapy (repeated ANOVA, P\xa0 Table . 1801P Longitudinal tracking of SNAP and SNCV among 55 patients (mean±SD) baseline 3rd 5th 7th 9th 11th 1 month after 12th cycle SNAP (μV) 14.2± 6.3 12.2± 4.8 11.9± 4.8 11.4± 5.7 10.7± 5.0 9.5± 4.9 9.0± 4.8 SNCV (m/s) 56.6± 4.0 55.9± 4.9 56.2± 4.8 56.2± 4.8 55.3± 4.4 55.4± 4.8 55.4± 4.6 Conclusions This POCD demonstrated SNAP-dominant neuropathy in patients who received PTX, suggesting axonal degeneration as a mechanism of CIPN. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure Y. Ando: Honoraria (self): Bristol-Myers Squibb Company; Honoraria (self): Sawai Pharmaceutical Co. Ltd.; Research grant / Funding (self): Mochida Pharmaceutical Co.,Ltd.; Honoraria (self), Research grant / Funding (self): Nippon Kayaku Co.,Ltd.; Honoraria (self), Research grant / Funding (self): Taiho Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.