title: Serum iron levels as a new biomarker in chemotherapy with leucovorin and fluorouracil plus oxaliplatin or leucovorin and fluorouracil plus irinotecan, with or without molecularly-targeted drugs.
abstract: Serum iron levels have been reported to increase following the administration of various anticancer drugs. An increase in serum iron levels during therapy with leucovorin and fluorouracil plus oxaliplatin (FOLFOX) or leucovorin and fluorouracil plus irinotecan (FOLFIRI) was also observed. The aim of this study was to investigate the correlation between serum iron levels and prognosis in advanced colorectal cancer (CRC) patients treated with FOLFOX/FOLFIRI ± molecularly-targeted drugs. Serum iron levels were measured prior to and at 48 h after treatment with FOLFOX/FOLFIRI ± molecularly-targeted drugs in 72 advanced CRC patients, all of whom succumbed to the disease between December, 2005 and February, 2012. No patients received radiotherapy. Taking the median rate of increase in serum iron levels as the cut-off value in each therapy, the patients were divided into cohort I (increase rate greater than the cut-off value in at least one therapy) or cohort II (increase rate less than the cut-off value in all therapies). The χ2test and the t-test were used to compare patient characteristics between the two cohorts. Prognosis was evaluated between the two cohorts using the Kaplan-Meier method, the log-rank test and the Cox proportional hazards regression analysis. No significant bias in patient characteristics (including the frequency of chemotherapy or number of patients treated with molecularly-targeted drugs) was observed between the two cohorts. Serum iron levels were transiently elevated following treatment (P<0.001), returning to baseline within 2 weeks. Median survival time (MST) in cohort I (n=44) and cohort II (n=28) was 430 and 377 days, respectively. The MST was significantly higher in cohort I (P=0.0382). The multivariate analysis identified a small increase in serum iron levels as an independent risk factor for overall survival (OS). These results suggest that serum iron levels may be used as a new predictive factor in FOLFOX/FOLFIRI ± molecularly-targeted drug therapy. Serum iron levels may therefore prove to be a useful and convenient biomarker for OS in CRC patients.
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Ochiai
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kitajima
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Nakatani
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Inou
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Shibata
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kishine
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Shougo
authors.initials: S
authors.lastname: Seo
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okubo
authors.affiliation: Department of Surgery, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Futagawa
authors.affiliation: Department of Pharmacy, Tobu Chiiki Hospital, Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Mashiko
authors.affiliation: Department of Host Defense and Biochemical Research, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Nagaoka
keywords: biomarker; chemotherapy; leucovorin and fluorouracil plus irinotecan; leucovorin and fluorouracil plus oxaliplatin; serum iron levels