Serum iron levels as a predictive factor in FOLFOX/FOLFIRI therapy.

Abstract

e14141 Background: Recently, it was reported that iron reduction was associated with lower cancer risk and mortality (Zacharski et al, J NATL CANCER I 2008). An increase in serum iron levels after administration of various anticancer drugs was reported (Follezou et al, NEOPLASMA 1985). We have also reported an increase in serum iron levels during FOLFOX and FOLFIRI therapies (ASCO 2009: #e15110). The aim of this study was to evaluate the correlation between prognosis and serum iron levels in advanced colorectal cancer (CRC) patients treated with FOLFOX ± bevacizumab (Bev) or FOLFIRI ± Bev. Methods: Serum iron, hemoglobin, AST and ALT serum levels were measured before and at 48 hr after treatment (FOLFOX4 ± Bev, FOLFIRI ± Bev, or FOLFIRI + cetuximab [Cet]) in 47 advanced CRC patients, all of whom died between Dec. 2005 and Sep. 2010. Using the median rate of increase in serum iron levels as the cut-off value in each therapy, these patients were categorized into a high group (increase rate over cut-off value in at least one therapy) and a low group (increase rate under the cut-off value in all therapies). Prognosis was evaluated between the 2 groups using the Kaplan-Meier method and the log rank test. Results: No significant changes in hemoglobin, AST or ALT serum levels were observed during treatment. Serum iron levels transiently increased at after treatment (48 hr), then returning to baseline within 2 weeks. Median rate of increase in serum iron levels at before and at 48 hr after FOLFOX4, FOLFIRI, FOLFOX4 + Bev, FOLFIRI + Bev, or FOLFIRI + Cet therapies was 217%, 348%, 200%, 434% and 344%, respectively, showing a significant increase (p<0.001). Median survival time (MST) in the high group (n: 28) and low group (n: 19) was 421.5 and 351 days, respectively. The MST was significantly better in the high group (p=0.036). Conclusions: The results suggest that transient increases in serum iron levels are not due to destruction of hepatocytes or erythrocytes. The significantly better prognosis in the high group suggests that serum iron levels could be used as a predictive factor in FOLFOX/FOLFIRI therapy.