Talboom Kevin, Borstlap Wernard A A, Roodbeen Sapho X, Bruns Emma R J, Buskens Christianne J, Hompes Roel, Tytgat Kristien M A J, Tuynman Jurriaan B, Consten Esther C J, Heuff Gijsbert, Kuiper Teaco, van Geloven Anna A W, Veldhuis Gerrit J, van der Hoeven Joost A B, Gerhards Michael F, Sietses Colin, Spinelli Antonino, van de Ven Anthony W H, van der Zaag Edwin S, Westerterp Marinke, van Westreenen Henderik L, Dijkgraaf Marcel L, Juffermans Nicole P, Bemelman Wilhelmus A
Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands.
Department of Gastroenterology, Amsterdam UMC, Location AMC, Amsterdam, Netherlands.
Lancet Haematol. 2023 Apr;10(4):e250-e260. doi: 10.1016/S2352-3026(22)00402-1. Epub 2023 Feb 27.
A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia.
In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1-2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment.
Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11-22) before surgery for intravenous iron and 19 days (IQR 13-27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55-2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87-4·58]; p<0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202).
Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation.
Vifor Pharma.
在高收入国家，三分之一符合手术条件的结直肠癌患者伴有贫血，这与不良预后相关。我们旨在比较术前静脉注射铁剂和口服铁剂对结直肠癌合并缺铁性贫血患者的疗效。
在FIT多中心、开放标签、随机对照试验中，计划进行择期根治性切除且患有缺铁性贫血（定义为女性血红蛋白水平低于7.5 mmol/L（12 g/dL），男性低于8 mmol/L（13 g/dL），转铁蛋白饱和度低于20%）的M0期成年结直肠癌患者（年龄18岁及以上）被随机分配接受1-2 g羧基麦芽糖铁静脉注射或每日三片200 mg口服富马酸亚铁治疗。主要终点是术前血红蛋白水平恢复正常（女性≥12 g/dL，男性≥13 g/dL）的患者比例。对主要分析进行意向性分析。对所有接受治疗的患者进行安全性分析。该试验已在ClinicalTrials.gov注册，编号为NCT02243735，且已完成招募。
在2014年10月31日至2021年2月23日期间，纳入202例患者并分配至静脉注射组（n = 96）或口服组（n = 106）接受铁剂治疗。静脉注射铁剂治疗在术前中位14天（IQR 11 - 22）开始，口服铁剂治疗在术前中位19天（IQR 13 - 27）开始。84例接受静脉注射治疗的患者中有14例（17%）在入院时血红蛋白恢复正常，97例接受口服治疗的患者中有15例（16%）在入院时血红蛋白恢复正常（相对风险[RR] 1.08 [95% CI 0.55 - 2.10]；p = 0.83），但静脉注射治疗组在后续时间点血红蛋白恢复正常的患者比例显著增加（30天时82例中有49例[60%]，而88例中有18例[21%]；RR 2.92 [95% CI 1.87 - 4.58]；p < 0.0001）。最常见的与治疗相关的不良事件是口服铁剂治疗后粪便变色（1级）（105例中有14例[13%]），两组均未观察到与治疗相关的严重不良事件或死亡。在其他安全性指标方面未观察到差异，最常见的严重不良事件是吻合口漏（202例中有11例[5%]）、吸入性肺炎（202例中有5例[2%]）和腹腔内脓肿（202例中有5例[2%]）。
两种治疗方案在术前血红蛋白恢复正常的情况均不常见，但静脉注射铁剂治疗后在所有其他时间点均有显著改善。仅静脉注射铁剂才能恢复铁储备。在选定患者中，可延迟手术以增强静脉注射铁剂对血红蛋白恢复正常的效果。
维福制药公司。
