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Bevacizumab Exacerbates Paclitaxel-Induced Neuropathy: A Retrospective Cohort Study.

Authors :
Ayumu Matsuoka
Osamu Maeda
Takefumi Mizutani
Yasuyuki Nakano
Nobuyuki Tsunoda
Toyone Kikumori
Hidemi Goto
Yuichi Ando
Source :
PLoS ONE, Vol 11, Iss 12, p e0168707 (2016)
Publication Year :
2016
Publisher :
Public Library of Science (PLoS), 2016.

Abstract

Bevacizumab (BEV), a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, enhances the antitumor effectiveness of paclitaxel (PTX)-based chemotherapy in many metastatic cancers. A recent study in mice showed that VEGF receptor inhibitors can interfere with the neuroprotective effects of endogenous VEGF, potentially triggering the exacerbation of PTX-induced neuropathy. In clinical trials, exacerbation of neuropathy in patients who received PTX combined with BEV (PTX+BEV) has generally been explained by increased exposure to PTX owing to the extended duration of chemotherapy. We investigated whether the concurrent use of BEV is associated with the exacerbation of PTX-induced neuropathy.Female patients with breast cancer who had received weekly PTX or PTX+BEV from September 2011 through May 2016 were studied retrospectively. PTX-induced neuropathy was evaluated at the same time points (at the 6th and 12th courses of chemotherapy) in both cohorts. A multivariate Cox proportional-hazards model was used to assess the independent effect of BEV on the time to the onset of neuropathy.A total of 107 patients (median age, 55 years; range, 32-83) were studied. Sixty-one patients received PTX as adjuvant chemotherapy, 23 received PTX for metastatic disease, and 23 received PTX+BEV for metastatic disease. Peripheral sensory neuropathy was worse in patients who received PTX+BEV than in those who received PTX alone: at the 6th course, Grade 0/1/2/3 = 4/13/4/0 vs. 25/42/6/0 (P = 0.095); at the 12th course, 2/3/11/3 vs. 7/30/23/2 (P = 0.016). At the 12th course, the incidence of Grade 2 or higher neuropathy was significantly higher in patients treated with PTX+BEV than in those treated with PTX alone (74% vs. 40%; P = 0.017). In multivariate analysis, BEV was significantly associated with an increased risk of neuropathy (HR 2.32, 95% CI 1.21-4.44, P = 0.012).The concurrent use of BEV could worsen PTX-induced neuropathy in patients with breast cancer.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
11
Issue :
12
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.5497265efae54bf7bb38b88f06c66f43
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0168707