Improvement in efficacy of chemoradiotherapy by addition of an antiangiogenic agent in a murine tumor model.
BACKGROUND
Chemoradiotherapy improves survival for some cancer patients. Methods of enhancing treatment response would further enhance survival rates. The effect of the addition of an antiangiogenic agent to a chemoradiotherapy regime has not previously been examined.


METHODS
C57B16 mice were inoculated with 1 x 10(6) Lewis lung carcinoma cells into the flank and randomized to 1 of 10 treatment groups when tumor volume approached 1000 mm(3). Animals received combinations of standard doses of intraperitoneal cisplatin, 5-fluorouracil, and the antiangiogenic agent genistein, together with 10 or 20 Gy of external beam radiotherapy. Animals were sacrificed at day 6 when tumor volume, microvessel density, and serum VEGF were determined.


RESULTS
Mean (SEM) tumor volume in the chemoradiotherapy group was 762 (212) mm(3) versus 565 (79) mm(3) in the chemoradiotherapy plus genistein group (P = 0.04, unpaired t-test). The addition of genistein produced a significant reduction in tumor microvessel density (P = 0.01) as well as serum VEGF levels (P < 0.05) compared to those animals receiving chemoradiation alone.


CONCLUSIONS
This study provides proof of principle that chemoradiation can be enhanced by the addition of an antiangiogenic agent to the regime and suggests that further examination of such regimes is warranted.
McDonnell
C O
CO
Department of Surgery, Royal College of Surgeons in Ireland, James Connolly Memorial Hospital, Blanchardstown, Ireland.
Holden
G
G
Sheridan
M E
ME
Foley
D
D
Moriarty
M
M
Walsh
T N
TN
Bouchier-Hayes
D J
DJ
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001808:Blood Vessels / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D019833:Genistein / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects; D009368:Neoplasm Transplantation; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D019833:Genistein; D002945:Cisplatin; D005472:Fluorouracil