Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study
Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study
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DOI：
10.1016/s1470-2045(07)70108-0
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发表时间：
2007-05-01
期刊：
影响因子：
51.1
通讯作者：
Van Cutsem, Eric
中科院分区：
文献类型：
--
作者：
Tejpar, Sabine;Piessevaux, Hubert;Van Cutsem, Eric
背景：初步证据表明，在使用表皮生长因子受体（EGFR）靶向抗体治疗结直肠癌的患者中发生镁消耗。这种副作用的机制尚不清楚，是否全部或部分患者受到影响也不清楚。我们旨在评估egfr靶向抗体治疗期间镁浪费的发生率、特征和预测因素，并研究这一现象的病理生理机制。方法：我们对98例接受egfr靶向抗体治疗或不接受联合化疗的结直肠癌患者的镁浓度进行了前瞻性测量。主要结局指标是血清镁浓度随时间的斜率。测定35例患者24 h尿镁排泄量。在一部分患者（n=5）中，进行了静脉镁负荷试验。单独接受化疗的16名患者作为对照。在研究开始之前，我们已经编写了一份临床方案，但由于这是一项非介入性研究，因此该方案没有正式注册。结果：与基线测量值相比，95例（97%）患者在egfr靶向治疗期间血清镁浓度下降。egfr靶向治疗期间（联合或不联合化疗）的平均血清镁斜率明显低于单独化疗(-0.00157 mmol/L/day, SD 0.00162 [95% CI -0.00191 ~ -0.00123] vs 0.00014 mmol/L/day, SD 0.00076 [-0.00026 ~ 0.00055]; （t检验，p < 0.0001）。24小时尿液分析和静脉镁负荷试验显示肾镁重吸收缺陷。egfr抑制抗体损害肾脏镁潴留能力，导致大多数患者出现低镁血症。未来的研究应该解决暴露和靶标亲和力的影响。我们的研究表明egfr信号通路在调节镁稳态中的关键作用。
Background Preliminary evidence suggests that magnesium wasting occurs in patients who are treated with epidermal-growth-factor receptor (EGFR)-targeting antibodies for colorectal cancer. The mechanism of this side-effect is unknown, and if all or a subset of patients are affected is also unclear. We aimed to assess the incidence, characteristics, and predictive factors of magnesium wasting during treatment with EGFR-targeting antibodies, and to study the pathophysiology of this phenomenon.Methods We measured prospectively magnesium concentrations in a cohort of 98 patients with colorectal cancer treated with EGFR-targeting antibodies with or without combined chemotherapy. The primary outcome measure was the slope of the serum magnesium concentrations overtime. In 3 5 patients, 24-h urinary magnesium excretion was measured. In a subset of patients (n=5), an intravenous magnesium load test was done. 16 patients who had chemotherapy alone acted as controls. A clinical protocol was written before initiation of the study, but because this was a non-interventional study, the protocol was not formally registered.Findings 95 (97%) patients had decreasing serum magnesium concentrations during EGFR-targeting treatment compared with baseline measurements. The mean serum magnesium slope during EGFR-targeting treatment (with or without combined chemotherapy) was significantly lower compared with chemotherapy alone (-0.00157 mmol/L/ day, SD 0.00162 [95% CI -0.00191 to -0.00123] vs 0.00014 mmol/L/day, SD 0.00076 [-0.00026 to 0.00055]; (t test, p < 0.0001). 24-h urine analysis and intravenous magnesium load tests showed a defect in renal magnesium reabsorption.Interpretation EGFR-inhibiting antibodies compromised the renal magnesium retention capacity, leading to hypomagnesaemia in most patients. Future studies should address the effects of exposure and target affinity. Our study suggests a pivotal role of the EGFR-signalling pathway in regulating magnesium homoeostasis.