Neoadjuvant chemotherapy including bevacizumab in potentially curable metastatic colorectal cancer

Abstract

3546 Background: the addition of targeting therapies to combination chemotherapy have dramatically improved outcome in metastatic colorectal cancer (mCRC). Special issues have been raised regarding the sequence of bevacizumab (bev) administration and surgery in mCRC. Methods: a pilot series of non-optimal resectable mCRC patients was initiated including a neoadjuvant protocol with bevacizumab 5mg/kg every two weeks plus XELOX (capecitabine 3500mg/m2/day days 1–7 plus oxaliplatin 85mg/m2 day 1 of a 2-week cycle) for six cycles (3 months). The sixth cycle did not include bev resulting in a gap of 5 weeks between last bev and surgery. Additional 6 cycles were started 5 weeks after surgery. Primary end points were feasibility of the regimen, possibility of curative surgical approach and morbidity of the surgical procedure including liver resection. Results: we have enrolled 22 patients of whom 12 are evaluable for all primary endpoints today. Median age of the patients was 61.5 years (± 8.8), 83% had a lymph node positive primary, 67% had synchronous liver metastases (LM), 33% had bilobar LM. The neoadjuvant treatment regimen was safely administered resulting in 2 CR, 8 PR and 2 SD; XELOX was dose reduced to 75% due to HFS, diarrhoe or PNP ≥ 3 in 3 patients (25%). Potentially curative surgery was performed in all but one patient (92%) including liver resection in 11 patients, involving additional resection of the primary in 3 patients. No patient required perioperative blood transfusions, morbidity consisted of one bile leak from the resection edge and one wound infection. No patient experienced bleeding complications or showed postoperative liver dysfunction. Median postoperative hospital stay was 7 days (± 1.7). All patients started adjuvant treatment within 5 weeks. Liver regeneration as evaluated during staging CTs confirmed no abnormalities. Conclusions: these data suggest that bevacizumab can be administered prior and after potentially curative surgery including liver resection without appearing to adversely effect surgical wound healing, bleeding or liver regeneration. However we would like to emphasize that patients need to be treated by an experienced multidisciplinary team including a liver surgeon qualified in dealing with chemotherapy altered livers. [Table: see text]