title: Bevacizumab Exacerbates Paclitaxel-Induced Neuropathy: A Retrospective Cohort Study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  The concurrent use of BEV could worsen PTX-induced neuropathy in patients with breast cancer.
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan.|Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Matsuoka
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Maeda
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Mizutani
authors.affiliation: Department of Clinical Oncology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tsunoda
authors.affiliation: Department of Breast and Endocrine Surgery, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Toyone
authors.initials: T
authors.lastname: Kikumori
authors.affiliation: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Goto
authors.affiliation: Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000068258:Bevacizumab / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D005260:Female; D006801:Humans; D051379:Mice; D008875:Middle Aged; D008954:Models, Biological; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control; D012189:Retrospective Studies
chemical_list: D000068258:Bevacizumab; D017239:Paclitaxel