Background: Type 2 diabetes mellitus (T2DM) is associated with increased risk of colon cancer (CC), whereas metformin use seems to be protective. However, the impact of metformin use on the risk of death or disease recurrence after radical surgery for CC remains uncertain.
Materials and methods: This is a substudy conducted in patients with high-risk stage II or stage III CC randomized in the TOSCA trial, which compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy. Objective of the study was to investigate the impact of metformin exposure during adjuvant chemotherapy on overall survival (OS) and relapse-free survival (RFS). We also evaluated the impact of T2DM or metformin dosage on clinical outcomes.
Results: Out of 3,759 patients enrolled in the TOSCA trial, 133 patients with diabetes (9.2%) and 1,319 without diabetes (90.8%) were recruited in this study. After excluding 13 patients with diabetes without information on metformin exposure, 76 patients with T2DM (63.3%) were defined as metformin users and 44 (36.7%) as metformin nonusers. After a median follow-up of 60.4 months, 26 (21.7%) patients relapsed and 16 (13.3%) died. Metformin use was neither associated with OS (adjusted hazard ratio [HR], 1.51; 95% confidence interval [CI], 0.48-4.77; p = .4781) nor with RFS (HR, 1.56; 95% CI, 0.69-3.54; p = .2881). Similarly, we found no association between T2DM or metformin dosage and OS or RFS.
Conclusions: Metformin use and T2DM did not impact on OS or RFS in patients with resected CC treated with adjuvant fluoropyrimidine-oxaliplatin chemotherapy. Larger studies and longer follow-up are required to clarify the potential efficacy of metformin in improving the prognosis of patients with CC.
Implications for practice: The role of the antidiabetic drug metformin in colon cancer prevention and treatment is highly debated. While low-dose metformin reduced the incidence of colorectal adenomas in two prospective studies, its effect in patients with already established colon cancer remains unclear. In this study, the potential impact of metformin on the survival of resected colon cancer patients who received adjuvant chemotherapy was investigated in the context of the TOSCA study. We did not find any association between metformin use or dosages and patient survival. Prospective studies are required to draw definitive conclusions about metformin impact on colon cancer recurrence and survival.
摘要
背景。2 型糖尿病 (T2DM) 与结肠癌 (CC) 风险增加有关，而二甲双胍的使用似乎具有保护作用。然而，二甲双胍的使用对 CC 根治性手术后死亡或疾病复发风险的影响仍不确定。
材料和方法。这是在 TOSCA 试验中随机分组的高风险 II 期或 III 期 CC 患者中进行的亚组研究，比较了 3 个月和 6 个月的氟尿嘧啶 ‐ 奥沙利铂辅助化疗。本研究的目的是调查辅助化疗期间二甲双胍暴露对总生存 (OS) 和无复发生存 (RFS) 的影响。我们还评估了 T2DM 或二甲双胍剂量对临床预后的影响。
结果。在参加 TOSCA 试验的 3 759 名患者中，本研究纳入了 133 名糖尿病患者(9.2%)和 1 319 名非糖尿病患者(90.8%)。排除 13 例无二甲双胍暴露信息的糖尿病患者后，76 例 T2DM 患者(63.3%)被定义为二甲双胍使用者，44 例(36.7%)为非二甲双胍使用者。 60.4 个月中位随访后，26 例(21.7%)患者复发，16 例(13.3%)死亡。二甲双胍的使用既不与 OS 相关 [校正风险比 (HR)，1.51；95% 置信区间 (CI)，0.48‐4.77；p = 0.478 1]，也不与 RFS 相关(HR，1.56；95% CI，0.69‐3.54；p = 0.288 1)。同样，我们发现 T2DM 或二甲双胍剂量与 OS 或 RFS 之间没有关联。
结论。在使用氟尿嘧啶 ‐ 奥沙利铂辅助化疗治疗已切除 CC 的患者中二甲双胍的使用和 T2DM 对 OS 或 RFS 没有影响。需要更大规模的研究和更长时间的随访来阐明二甲双胍在改善 CC 患者预后方面的潜在功效。
实践意义:抗糖尿病药物二甲双胍在结肠癌预防和治疗中的作用备受争议。虽然低剂量二甲双胍在两项前瞻性研究中降低了结直肠腺瘤的发病率，但其对已经确诊的结肠癌患者的影响尚不明确。本研究在 TOSCA 研究的背景下调查了二甲双胍对接受辅助化疗的已切除结肠癌患者存活率的潜在影响。我们未发现二甲双胍的使用或剂量与患者存活率之间存在任何关联。需要前瞻性研究以得出关于二甲双胍对结肠癌复发和生存率的影响的确切结论。
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