Bevacizumab protects against sinusoidal obstruction syndrome and does not increase response rate in neoadjuvant XELOX/FOLFOX therapy of colorectal cancer liver metastases.
OBJECTIVE
In patients suffering from colorectal cancer liver metastases, 5-fluorouracil-based chemotherapy plus oxaliplatin ensures superior response rates at the cost of hepatic injury. Knowledge about the consequences of bevacizumab on chemotherapy-induced hepatic injury and tumor response is limited.


METHODS
Resected liver specimens from patients of two prospective, non-randomized trials (5-fluorouracil/oxaliplatin+/-bevacizumab) were analyzed retrospectively. Hepatotoxicity to the non-tumor bearing liver was evaluated for sinusoidal obstruction syndrome, hepatic steatosis and fibrosis. Tumor response under chemotherapy was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST).


RESULTS
Bevacizumab decreased the severity of the sinusoidal obstruction syndrome. Bevacizumab had no impact on hepatic steatosis and fibrosis. The addition of bevacizumab to chemotherapy had no effect on tumor response compared to combination chemotherapy alone.


CONCLUSIONS
This analysis shows that bevacizumab protects against the sinusoidal obstruction syndrome and thus provides the histological explanation of the safe use of bevacizumab prior to liver resection. Furthermore, we show that bevacizumab does not improve tumor response according to RECIST.
Klinger
M
M
Department of General Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. markus.klinger@meduniwien.ac.at
Eipeldauer
S
S
Hacker
S
S
Herberger
B
B
Tamandl
D
D
Dorfmeister
M
M
Koelblinger
C
C
Gruenberger
B
B
Gruenberger
T
T
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D000069287:Capecitabine; D016009:Chi-Square Distribution; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000473:pathology*; D003841:Deoxycytidine / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006504:Hepatic Veno-Occlusive Disease / Q000517:prevention & control*; D006801:Humans; D002955:Leucovorin; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D012044:Regression Analysis; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil