Bevacizumab Treatment Before Resection of Colorectal Liver Metastases: Safety, Recovery of Liver Function, Pathologic Assesment.

Patients with metastatic colorectal cancer receive chemotherapy prior liver resection more and more frequently. This preoperative treatment has many effects which have to be analysed, like the safety of liver resection, toxicity, tissue regeneration, radiological and pathological response and survival data. The aim of the study was to evaluate the safety of bevacizumab containing preoperative chemotherapy and functional recovery of the liver after resection for colorectal liver metastases (CLM) and to analyse radiological and pathological data. Data of three groups of 120 consecutive patients-(1) CTX + BV: cytotoxic chemotherapy + bevacizumab, (2) CTX: cytotoxic chemotherapy, (3) NC: no treatment before liver resection-were analysed. Postoperative liver function and complications were compared, clinical, radiological and pathological data were evaluated. Between 01.12.2006 and 31.12.2010 41 resections was performed after chemotherapy + bevacizumab (CTX + BV) and 27 resections was performed after preoperative chemotherapy without bevacizumab (CTX). There were 60 hepatic resections in this period without neoadjuvant treatment (NC). 8 patients had repeated resections. The postoperative complication rate was 40 % but there was no statistical difference between the groups (P = 0.72). Only the type of resection was associated with a significantly higher complication rate (p = 0.03). The subgroup of patients, who received irinotecan had a higher complication rate in the CTX group than in the BV + CTX group (55 % vs 41 %). Preoperative administration of bevacizumab was associated with higher peak postoperative AST, ALT levels but did not affect functional recovery of the liver. The RECIST system was not able to predict the outcome after chemotherapy in every patient and in many cases this system overestimated the effect of chemotherapy. On histopathological examination the presence of necrosis was not associated with chemotherapy or pathological response. Use of chemotherapy before hepatic resection of CLM was not associated with a significant increase in complication rates. The functional recovery of the liver was not affected by the preoperative administration of chemotherapy. The use of combined neoadjuvant chemotherapy is safe before hepatic resection

Histopathologic evaluation of liver metastases from colorectal cancer in patients treated with FOLFOXIRI plus bevacizumab.

BACKGROUND: The FOLFOXIRI regimen produces a high rate of radiological and histopathological responses. Bevacizumab added to chemotherapy showed an improvement in pathological response and necrosis of colorectal liver metastases (CLMs). FOLFOXIRI plus bevacizumab produced promising early clinical results and is under investigation in several randomised trials, although no data are currently available on its effects on response of CLMs and on liver toxicities. METHODS: Starting from 499 patients enrolled in first-line phase II/III trials, we selected on the basis of tissue sample availability 18 patients treated with FOLFOXIRI/XELOXIRI and 24 patients treated with FOLFOXIRI plus bevacizumab who underwent secondary resection of CLMs. The 28 untreated patients who underwent primary resection of CLMs were included as control group. Responses of CLMs and chemotherapy-induced toxicities were assessed. RESULTS: Among the patients, 63% of those treated with FOLFOXIRI plus bevacizumab, as compared with 28% of those treated with only FOLFOXIRI/XELOXIRI, showed a histopathological response (P=0.033). In the two groups, 52% and 12.5%, respectively, showed necrosis ⩾50% (P=0.017). The incidence of liver toxicities was not significantly increased in patients treated with FOLFOXIRI plus bevacizumab. CONCLUSION: The addition of bevacizumab to FOLFOXIRI produces high rates of pathologic responses and necrosis of CLM without increasing liver toxicity