Abstract 856
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 < 0.001), whereas there was no significant change in SNCV (Table). The total sum of SNAP (mean±SD) was 91.7±30.6 in G1, 70.5±30.0 in G2, and 41.4±13.1 in G3. The total sum of SNCV (mean±SD) was 393.5±34.0 in G1, 381.4±39.5 in G2, and 370.1±45.3 in G3. The total SNAP differed significantly according to each CTCAE grade (ANOVA, P < 0.001), whereas the total SNCV did not.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.
Clinical trial identification
Editorial acknowledgement
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.
Resources from the same session
3620 - Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
Presenter: Wolfgang Wick
Session: Poster Display session 1
Resources:
Abstract
5465 - Proof of concept clinical study by US-guided intratumor injection of VCN-01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer
Presenter: Manuel Hidalgo
Session: Poster Display session 1
Resources:
Abstract
2555 - A Phase 1a/b first-in-human, open-label, dose-escalation, safety, PK and PD study of TP-0903 in solid tumors
Presenter: John Sarantopoulos
Session: Poster Display session 1
Resources:
Abstract
3533 - First in human phase 1/2a study of PEN-866, a Heat Shock Protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumors: Phase 1 results
Presenter: Johanna Bendell
Session: Poster Display session 1
Resources:
Abstract
4114 - A Phase I Open-Label, Non-Randomized Study of Recombinant Super-Compound Interferon (rSIFN-co) In Patients with Advanced Solid Tumors
Presenter: Amanda Seet
Session: Poster Display session 1
Resources:
Abstract
2537 - Evaluation of Pharmacodynamic (PD) Biomarkers in Advanced Cancer Patients Treated with Oxidative Phosphorylation (OXPHOS) Inhibitor, OPC-317 (OPC)
Presenter: Jie Qing Eu
Session: Poster Display session 1
Resources:
Abstract
5764 - Pharmacokinetic (PK) assessment of BT1718: A phase 1/2a study of BT1718, a first in class Bicycle Toxin Conjugate (BTC), in patients (pts) with advanced solid tumours
Presenter: Natalie Cook
Session: Poster Display session 1
Resources:
Abstract
2683 - A phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumors.
Presenter: Wael Harb
Session: Poster Display session 1
Resources:
Abstract
3609 - Interim Results from Trial of SL-801, a Novel XPO-1 Inhibitor, in Patients with Advanced Solid Tumors
Presenter: Judy Wang
Session: Poster Display session 1
Resources:
Abstract
3485 - Phase 1 Trial of Fruquintinib in Patients with Advanced Solid Tumors: Results of the Dose Escalation Phase
Presenter: Andrea Wang-Gillam
Session: Poster Display session 1
Resources:
Abstract