Abstract
BackgroundBevacizumab (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.MethodsFemale 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.ResultsA 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).ConclusionsThe concurrent use of BEV could worsen PTX-induced neuropathy in patients with breast cancer.
Highlights
Bevacizumab (BEV), a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), enhances the antitumor effectiveness of standard chemotherapy in various metastatic cancers, including cancer of the breast, colon, lung and ovary [1]
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
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)
Summary
Bevacizumab (BEV), a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF), enhances the antitumor effectiveness of standard chemotherapy in various metastatic cancers, including cancer of the breast, colon, lung and ovary [1]. The incidence of neuropathy was reported to be higher in patients who had received PTX combined with BEV (PTX+BEV) than in those who had received PTX alone [2] This exacerbation of neuropathy has generally been explained by the prolonged exposure to PTX owing to the extended duration of chemotherapy [3]. BEV is generally considered to be unrelated to peripheral neuropathy [1, 4] It is unclear whether the concurrent use of BEV is associated with the exacerbation of PTX-induced neuropathy. 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
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
