Neoadjuvant Bevacizumab (Avastin) Safe for Colorectal Cancer Liver Metastases

There were no unexpected bleeding complications when neoadjuvant bevacizumab (Avastin) was given before curative resections of liver metastases from colorectal cancer, researchers reported here.
Moreover, bevacizumab treatment up to five weeks before surgery did not adversely affect regeneration of liver tissue following surgery, found Thomas Gruenberger, M.D., of the at the Medical University Hospital in Vienna, Austria.
In a 56-patients phase II study "neither the rate of surgical or wound healing complications nor the severity of bleeding were increased compared with historical data of chemotherapy alone," said Dr. Gruenberger at the American Society of Clinical Oncology meeting.
The median age of the patients was 61.5, and 32 of the patients were men. There were 34 patients with node-positive tumors, as well as 34 patients with synchronous liver metastases, and 29 patients had bilirubinemia.
He said the data "demonstrate that with appropriate management, bevacizumab can be used in combination with chemotherapy, with minimal risk of bleeding and wound-healing complications, in patients with metastatic colorectal cancer and liver metastases undergoing liver resection."
Dr. Gruenberger said that chemotherapy prior to surgery has the theoretical advantages of destroying micrometastases, thereby reducing the risk of recurrence, and can downsize tumors, which could make the chances of complete resection more viable.
However, the use of bevacizumab in combination with resection in the highly vascular liver has not been attempted with great frequency so that the risks of the use of the agent prior to surgery were not known.
The neoadjuvant regimen combined bevacizumab at 5 mg/kg every two weeks plus capecitabine (Xelox) at 3,500 mg/m2/day for one week plus oxaliplatin (Eloxatin) at 85 mg/m2 of the first day of a two-week cycle), for six cycles of treatment before attempting surgery. The regimen was resumed five weeks after surgery and continued for six more cycles.
Within the cohort, 41 patients had liver resection surgery only, while 11 patients had synchronous primary as well as liver resection, he said.
Of the four patients who did not have surgery one patient had it suspended because of extrahepatic disease during laparotomy. The other three did not undergo surgery because of progressive disease and so received second-line therapy, Dr. Gruenberger said at his poster presentation.
Among the findings:
There was no peri-operative mortality.
Three patients required blood transfusions.
One patient required additional surgery to close a small bowel perforation.
Three patients developed sepsis, two developed hyperbilirubinemIa, one patient developed a wound infection, and one developed a wound hematoma.
Forty patients responded and 11 had stable disease
"Our data support a previous Phase I trial that showed that a regimen of bevacizumab plus chemotherapy and radiation therapy used seven weeks prior to surgery, in patients with advanced rectal cancer, resulted in no apparent effects on wound healing or bleeding," he said.