Long-course preoperative chemotherapy did not improve response in liver metastases

2009 Gastrointestinal Cancers Symposium

Patients with colorectal liver metastases treated with extended preoperative chemotherapy (nine or more cycles) experienced increased incidence of liver insufficiency without improved pathologic response, according to the results of a study presented by Daria Zorzi, MD, a research fellow in surgical oncology at The University of Texas M.D. Anderson Cancer Center, at the 2009 Gastrointestinal Cancers Symposium in San Francisco.

Researchers selected 219 patients, who underwent preoperative FOLFOX with or without bevacizumab (Avastin, Genentech) prior to hepatic resection for colorectal liver metastases.

“The aim of the study was to assess the association between preoperative chemotherapy and pathologic response and hepatic insufficiency after resection of liver metastases,” Zorzi told HemOnc Today.

Patients were divided in two groups according to the duration of chemotherapy: one to eight cycles of chemotherapy (n=157) or to nine or more cycles (n=62).

“Extended chemotherapy was not correlated with an increased pathologic response,” Zorzi said. Pathologic response rate was 57% in the short-course group vs. 55% in the long-course group (P=.738).

Forty-two percent of patients in the long-course group had sinusoidal injury compared with 26% in the short-course group (P=.017). Patients in the long-course group also experienced a statistically significant higher rate of liver insufficiency (11% vs. 4%). Multivariate analysis showed that only duration of chemotherapy acted as an independent predictor for liver insufficiency. – by Jason Harris

Zorzi et al asked three major questions: Is long-course chemotherapy vs. short-course associated with an increased pathological response? Is long course vs. short course associated with greater liver injury? Lastly, what does bevacizumab add vis-à-vis toxicity and efficacy? The answers to these questions are important and relevant. First, longer duration of chemotherapy does not increase pathologic response, only liver injury. Second, bevacizumab may alter liver injury. This was surprising to me, ie, less sinusoidal injury but a trend toward more liver insufficiency. This needs to be explored further. Third, the addition of bevacizumab increases the pathologic response rate. Whether this last point matters is the subject of some debate. I am not sure how much it matters as this surrogate endpoint has not yet been validated. Nevertheless, this M.D. Anderson Cancer Center experience, along with other bevacizumab experiences that have been reported, provide enough rationale to move forward with the testing of bevacizumab in large, multi-institutional, phase-3 studies for patients with resectable disease.

– David P. Ryan, MD

Clinical Director of the Tucker Gosnell Center for Gastrointestinal Cancers
Massachusetts General Hospital Cancer Center

For more information:

Zorzi D. #295. Presented at: the 2009 Gastrointestinal Cancers Symposium; Jan. 15-17, 2009; San Francisco.