PURPOSE: Bevacizumab, a monoclonal antibody that binds to VEGF, has a well-known toxic effect of hypertension. We studied possible associations between bevacizumab-related hypertension and gene polymorphisms to assure safer cancer therapy. METHODS: We retrospectively studied 60 Japanese patients with metastatic colorectal cancer who had received bevacizumab-based chemotherapy. Genotypes were determined for five well-known functional single-nucleotide polymorphism of the VEGF gene at positions C-2578A, T-1498C, G-1154A, G-634C, and C936T. Hypertension was graded according to CTCAE v4.0 on the basis of home blood pressure. RESULTS: The VEGF-2578 C/C and -1498 T/T genotypes were associated with significantly less hypertension during the first 2 months of bevacizumab-based chemotherapy (p = 0.004, p = 0.025, respectively). During the treatment period as a whole, the VEGF-2578 C/C and 936 C/C genotypes were associated with less hypertension (p = 0.031, p = 0.043, respectively). Preexisting hypertension was not associated with bevacizumab-related hypertension. CONCLUSIONS: This study demonstrated a significant relation between a lower incidence of grade 2 or higher bevacizumab-related hypertension and the VEGF-2578 C/C genotype for the entire treatment period in Japanese patients with metastatic colorectal cancer. This genotype might be useful for ensuring safer treatment of patients who receive bevacizumab-based chemotherapy.
PURPOSE:Bevacizumab, a monoclonal antibody that binds to VEGF, has a well-known toxic effect of hypertension. We studied possible associations between bevacizumab-related hypertension and gene polymorphisms to assure safer cancer therapy. METHODS: We retrospectively studied 60 Japanese patients with metastatic colorectal cancer who had received bevacizumab-based chemotherapy. Genotypes were determined for five well-known functional single-nucleotide polymorphism of the VEGF gene at positions C-2578A, T-1498C, G-1154A, G-634C, and C936T. Hypertension was graded according to CTCAE v4.0 on the basis of home blood pressure. RESULTS: The VEGF-2578 C/C and -1498 T/T genotypes were associated with significantly less hypertension during the first 2 months of bevacizumab-based chemotherapy (p = 0.004, p = 0.025, respectively). During the treatment period as a whole, the VEGF-2578 C/C and 936 C/C genotypes were associated with less hypertension (p = 0.031, p = 0.043, respectively). Preexisting hypertension was not associated with bevacizumab-related hypertension. CONCLUSIONS: This study demonstrated a significant relation between a lower incidence of grade 2 or higher bevacizumab-related hypertension and the VEGF-2578 C/C genotype for the entire treatment period in Japanese patients with metastatic colorectal cancer. This genotype might be useful for ensuring safer treatment of patients who receive bevacizumab-based chemotherapy.
Authors: Megan Li; Flora Mulkey; Chen Jiang; Bert H O'Neil; Bryan P Schneider; Fei Shen; Paula N Friedman; Yukihide Momozawa; Michiaki Kubo; Donna Niedzwiecki; Howard S Hochster; Heinz-Josef Lenz; James N Atkins; Hope S Rugo; Susan Halabi; William Kevin Kelly; Howard L McLeod; Federico Innocenti; Mark J Ratain; Alan P Venook; Kouros Owzar; Deanna L Kroetz Journal: Clin Cancer Res Date: 2018-06-05 Impact factor: 12.531
Authors: Julia C F Quintanilha; Jin Wang; Alexander B Sibley; Chen Jiang; Amy S Etheridge; Fei Shen; Guanglong Jiang; Flora Mulkey; Jai N Patel; Daniel L Hertz; Elizabeth Claire Dees; Howard L McLeod; Monica Bertagnolli; Hope Rugo; Hedy L Kindler; William Kevin Kelly; Mark J Ratain; Deanna L Kroetz; Kouros Owzar; Bryan P Schneider; Danyu Lin; Federico Innocenti Journal: Br J Cancer Date: 2021-10-06 Impact factor: 9.075
Authors: Jaime Feliu; Antonieta Salud; Maria J Safont; Carlos García-Girón; Jorge Aparicio; Ferran Losa; Carlos Bosch; Pilar Escudero; Enrique Casado; Monica Jorge; Uriel Bohn; Ramon Pérez-Carrión; Alberto Carmona; Ana B Custodio; Joan Maurel Journal: PLoS One Date: 2015-01-20 Impact factor: 3.240