Nab-paclitaxel efficacy in the orthotopic model of human breast cancer is significantly enhanced by concurrent anti-vascular endothelial growth factor A therapy.
Nab-paclitaxel is an albumin-bound 130-nm particle form of paclitaxel that has shown an improved efficacy in experimental tumor models and clinical studies compared with solvent-based paclitaxel. Anti-vascular endothelial growth factor A (VEGF-A) antibody bevacizumab is known to enhance antitumor activity of cytotoxic drugs. This study evaluated the effects of combined nab-paclitaxel and bevacizumab therapy on growth and metastatic spread of orthotopic breast tumors. Cytotoxic and clonogenic assays measured VEGF-A-dependent modulation of nabpaclitaxel toxicity on cultured tumor cells. Antitumor effects were assessed in mice with luciferase-tagged, well-established MDA-MB-231 tumors (250-310 mm3) treated with one, two, or three cycles of nab-paclitaxel (10 mg/kg, daily for five consecutive days), bevacizumab (2-8 mg/kg, twice a week), or with combination of both drugs. VEGF-A protected MDA-MB-231 cells against nab-paclitaxel cytotoxicity, whereas bevacizumab sensitized cells to the effect of the drug. Combined bevacizumab and nab-paclitaxel treatment synergistically inhibited tumor growth and metastasis resulting in up to 40% of complete regressions of well-established tumors. This therapy also decreased the incidence of lymphatic and pulmonary metastases by 60% and 100%, respectively. The significant increase in the cure of tumor-bearing mice in the nab-paclitaxel/bevacizumab combined group compared with mice treated with single drugs strongly advocates for implementing such strategy in clinics.
Volk
Lisa D
LD
Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, 801 N Rutledge, Springfield, IL, 62794-9678, USA.
Flister
Michael J
MJ
Bivens
Christopher M
CM
Stutzman
Alan
A
Desai
Neil
N
Trieu
Vuong
V
Ran
Sophia
S
D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000627:therapeutic use*
C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D008156:Luciferases; D017239:Paclitaxel