Targeted molecular therapies (cetuximab and bevacizumab) do not induce additional hepatotoxicity: preliminary results of a case-control study.
OBJECTIVE
To analyse the effects of the preoperative targeted molecular therapy (cetuximab (cetu) or bevacizumab (beva)) on non-tumorous liver parenchyma, and the clinical and biological outcome after liver resection for colorectal liver metastases (CLM).


METHODS
Between January 2005 and December 2007, 36 patients receiving preoperatively cetu (n = 15) or beva (n = 21) were, respectively, matched to a control group of patients who did not receive targeted molecular therapy. They were matched on the basis of age, gender, body mass index, extent of hepatectomy, and type and number of neoadjuvant chemotherapy. Liver function tests, postoperative outcome and histopathology of the resected liver were compared.


RESULTS
There was no mortality. Postoperative morbidity and perioperative bleeding rates were similar in both groups. In the beva group, liver function tests showed higher serum bilirubin level on postoperative day (POD) 1 (p = 0.001) and POD 3 (p = 0.01), higher serum aspartate aminotransferase on POD 1 (p = 0.004), and lower prothrombin time on POD 5 (p = 0.02). In both groups, cetu and beva, the postoperative peaks of gamma-glutamyl transpeptidase and alkaline phosphatase were statistically higher than in the control groups. Interestingly, the prevalence of sinusoidal injury and fibrosis was lower in patients receiving cetu (p = 0.04), while the prevalence of steatohepatitis was lower in patients receiving beva (p = 0.04).


CONCLUSIONS
The addition of beva or cetu to the neoadjuvant chemotherapy regimens does not appear to increase the morbidity rates after hepatectomy for CLM. The pathological examination did not show additional injury to the non-tumorous liver parenchyma.
Pessaux
P
P
Centre de Chirurgie Viscérale et de Transplantation - Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg - Université de Strasbourg, Avenue Molière, 67098 Strasbourg, France. patrick.pessaux@chru-strasbourg.fr <patrick.pessaux@chru-strasbourg.fr>
Panaro
F
F
Casnedi
S
S
Zeca
I
I
Marzano
E
E
Bachellier
P
P
Jaeck
D
D
Chenard
M P
MP
D000367:Age Factors; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D015992:Body Mass Index; D016022:Case-Control Studies; D000068818:Cetuximab; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006498:Hepatectomy; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011183:Postoperative Complications / Q000453:epidemiology; D012737:Sex Factors; D018709:Statistics, Nonparametric
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil