Serum iron levels potential biomarker in FOLFOX/FOLFIRI with or without molecularly targeted drug therapy.

Abstract

e14651 Background: We reported an increase in serum iron levels during therapy with FOLFOX or FOLFIRI ± molecularly targeted drugs and a correlation between prognosis and transition of those levels in advanced colorectal cancer (CRC) patients (ASCO; 2009: #e15110, 2011: #e14141, 2012: #e14004). The aims of this prospective cohort study were to establish serum iron levels as a new biomarker in advanced CRC patients undergoing therapy based on this correlation and investigate the mechanism of this increase in serum iron levels. Methods: Eighty-one advanced CRC patients were treated; all died between Dec. 2005 and Nov. 2012; none received radiotherapy; 9 of these patients were undergoing treatment between Sep. 2012 and Nov. 2012. Serum iron levels were measured at before and 48 hr after treatment. Taking the median rate of increase in serum iron levels as the cut-off value in each therapy, the patients were categorized into cohort I (increase rate over cut-off value in at least one therapy) or cohort II (increase rate under cut-off value in all therapies). Prognosis was evaluated between the two. Hepcidin (Hepc), Interleukin-6 (IL-6) and soluble transferrin receptor (sTfR) were measured at before and 48 hr after treatment. Results: No significant bias in patient characteristics (including in frequency or type of regimen) was observed between the two cohorts. Serum iron levels transiently increased after treatment (p<0.001), then returning to baseline within 2 weeks. Median survival time (MST) in cohort I (n: 50) and cohort II (n: 31) was 437 and 378 days, respectively, with MST significantly better in cohort I (p=0.0417). Multivariate analysis identified Dukes’ stage, recurrence type, and serum iron level as independent risk factors for overall survival (OS). Hepc significantly increased after treatment (p<0.001), with no significant change in IL-6 or sTfR. Conclusions: Serum iron levels offer potential as an extremely useful and convenient biomarker for OS in CRC patients. While Hepc significantly increased, no significant decrease was observed in sTfR after treatment. This suggests that serum iron levels increased as a result of a treatment-induced reduction in iron consumption by bone marrow.