Background: Folate level was proposed to be a predictor for fluoropyrimidine-related toxicity. We conducted a prospective study to determine the association between serum and red-cell folate and capecitabine-related toxicity in patients with colorectal cancers.
Materials and methods: Eligibility criteria included diagnosis of colorectal cancers; eligible patients who were scheduled to undergo capecitabine monotherapy or capecitabine-oxaliplatin (CAPOX) for adjuvant or palliative purposes. Exclusion criteria included concomitant radiotherapy or chemotherapy other than capecitabine or CAPOX and creatinine clearance <30 mL/min. Fasting serum and red-cell folate were measured prior to chemotherapy. Capecitabine was administered at 2,500 mg/m2 per day (monotherapy) or 2,000 mg/m2 per day (CAPOX) for 14 days every 3 weeks. The toxicity of the first four cycles was documented by clinical investigators who were blinded to folate levels.
Results: A total of 144 patients were recruited, of whom 126 were eligible; 40 patients had capecitabine alone, and 86 patients received CAPOX. The rates of grade 2 and grade 3 toxicity were 63.5% and 14.3%, respectively. Nausea and vomiting were the most common grade ≥2 adverse event (47.7%), followed by hand-foot syndrome (25.4%), diarrhea (23.1%), and neutropenia (22.3%). Combination with oxaliplatin (odds ratio [OR], 2.77; p = .043) and serum folate (OR, 10.33; p = .002) were independent predictors of grade ≥2 toxicity. Red-cell folate was not predictive of toxicity. For every 10 nmol/L increment in serum folate, the risk of grade ≥2 toxicity increased by 9%.
Conclusion: Serum folate level, but not red-cell folate, was associated with higher rate of grade ≥2 toxicity during capecitabine-based treatment. Excessive folate intake may be avoided before and during capecitabine-based chemotherapy.
Implications for practice: This is the first prospective study to evaluate the association between serum folate level and capecitabine-related toxicity in patients with colon cancers. It shows that higher serum folate level is associated with increased risks of moderate to severe toxicity during capecitabine-based treatment. Excessive folate intake should be avoided before and during capecitabine-based chemotherapy.
摘要
背景。有人提出将叶酸水平用作氟尿嘧啶相关毒性的预测因素。我们进行了一项前瞻性研究,旨在确定结直肠癌患者中的血清和红细胞叶酸与卡培他滨相关毒性之间的关系。
材料和方法。入选标准包括确诊结直肠癌;计划接受卡培他滨单药治疗或者卡培他滨‐奥沙利铂 (CAPOX) 辅助治疗或姑息治疗的符合条件的患者。排除标准包括除卡培他滨或 CAPOX 治疗之外的同步放疗或化疗以及肌酐清除率<30 mL/min。在化疗之前测量空腹血清和红细胞叶酸。卡培他滨每3周给药14 天,每天给药剂量为 2 500 mg/m2(单药治疗)或 2 000 mg/m2(CAPOX 治疗)。由不知晓叶酸水平的临床研究人员记录前四个周期的毒性情况。
结果。一共招募 144 名患者,其中,126 名患者符合条件;40 名患者接受卡培他滨单药治疗,86 名患者接受CAPOX 治疗。2 级和 3 级毒性的比率分别为 63.5% 和 14.3%。最常见的 >2 级的不良反应为恶心和呕吐 (47.7%),其次是手足综合征 (25.4%)、腹泻 (23.1%) 以及嗜中性白血球减少症 (22.3%)。联合奥沙利铂[比值比(OR],2.77;p=0.043)和血清叶酸(OR,10.33;p=0.002)是 >2 级毒性的独立预测因素。红细胞叶酸不能预测毒性。血清叶酸每增加10 nmol/L,>2 级毒性的风险就会升高9%。结论。在基于卡培他滨的治疗期间,血清叶酸水平(而非红细胞叶酸)与 >2 级毒性的较高比率相关。在基于卡培他滨的化疗之前及期间,可以避免摄入过多的叶酸
Keywords: Clinical predictors; Colon cancers; Complications; Folic acid; Prospective.
© AlphaMed Press 2018.