Antitumor activity of capecitabine and bevacizumab combination in a human estrogen receptor-negative breast adenocarcinoma xenograft model.
BACKGROUND
Capecitabine and bevacizumab have each been shown to inhibit tumor growth. Their combination failed to improve survival in a phase III trial of metastatic breast cancer (MBC), although it should be noted patients had been heavily pretreated with anthracyclines and taxanes. Our aim was to evaluate whether combination treatment would increase tumor growth inhibition and survival in a breast cancer model.


METHODS
Mice bearing KPL-4 human estrogen receptor-negative breast adenocarcinoma xenografts were given capecitabine orally daily for 14 days at the maximum tolerated dose (MTD) or half MTD, alone or with 5 mg/kg intraperitoneal bevacizumab twice weekly.


RESULTS
Tumor growth inhibition (TGI) and increased life span (ILS) were superior in the combination groups versus monotherapy (p < 0.05). TGI and ILS were significantly improved in the high- versus low-dose capecitabine combination (p < 0.05).


CONCLUSIONS
Capecitabine in combination with bevacizumab provides a basis for pursuing the combination for first-line treatment of MBC.
Higgins
Brian
B
Departments of Discovery Oncology, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. brian_x.higgins@roche.com
Kolinsky
Kenneth
K
Linn
Michael
M
Adames
Violeta
V
Zhang
Yu-E
YE
Moisa
Carlos
C
Dugan
Ute
U
Heimbrook
David
D
Packman
Kathryn
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000633:toxicity; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069287:Capecitabine; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000096:biosynthesis; D000068878:Trastuzumab; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011960:Receptors, Estrogen; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000068878:Trastuzumab; D017239:Paclitaxel; D005472:Fluorouracil