Sex moderates circadian chemotherapy effects on survival of patients with metastatic colorectal cancer: a meta-analysis
Sex moderates circadian chemotherapy effects on survival of patients with metastatic colorectal cancer: a meta-analysis
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DOI：
10.1093/annonc/mds148
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发表时间：
2012-12-01
影响因子：
50.5
通讯作者：
Levi, F.
中科院分区：
文献类型：
--
作者：
Giacchetti, S.;Dugue, P. A.;Levi, F.
分子生物钟可以改变癌症化疗的效果，并可能根据性别差异进行调节。我们研究了性别是否决定了转移性结直肠癌化疗的最佳给药方案。使用来自三项国际 III 期试验的个体数据进行了荟萃分析，这些试验比较了按时间调节 (chronoFLO) 或常规 (CONV) 输注给药的 5-氟尿嘧啶、亚叶酸和奥沙利铂。 345 名女性和 497 名男性的数据在 9 岁时更新。主要终点是生存率。与 CONV 相比，使用 chronoFLO 的男性总体生存率有所提高（P = 0.009），中位值为 20.8（95% CL，18.7 至 22.9）和 17.5 个月（16.1 至 18.8）。相反，女性中 chronoFLO 组的中位生存期为 16.6 个月（13.9 至 19.3），CONV 组的中位生存期为 18.4 个月（16.6 至 20.2）（P = 0.012）。性别与时间表的相互作用是最佳治疗方案的强有力的预测因素，在多变量分析中，总生存期的风险比为 1.59（1.30 至 1.75）（P = 0.002）。与传统化疗相比，男性接受时间调节化疗的寿命明显更长。目前的 chronoFLO 方案值得前瞻性评估，作为男性患者比传统分娩更安全、更有效的一线治疗选择。
Molecular circadian clocks can modify cancer chemotherapy effects, with a possible moderation according to sex differences. We investigated whether sex determine the optimal delivery schedule of chemotherapy for metastatic colorectal cancer.A meta-analysis was performed using individual data from three international Phase III trials comparing 5-fluorouracil, leucovorin and oxaliplatin administered in chronomodulated (chronoFLO) or conventional (CONV) infusions. The data from 345 females and 497 males were updated at 9 years. The main end point was survival.Overall survival was improved in males on chronoFLO when compared with CONV (P = 0.009), with respective median values of 20.8 (95% CL, 18.7 to 22.9) and 17.5 months (16.1 to 18.8). Conversely, median survival was 16.6 months (13.9 to 19.3) on chronoFLO and 18.4 months (16.6 to 20.2) on CONV in females (P = 0.012). The sex versus schedule interaction was a strong predictive factor of optimal treatment schedule, with a hazard ratio of 1.59 (1.30 to 1.75) for overall survival (P = 0.002) in multivariate analysis.Males lived significantly longer on chronomodulated chemotherapy rather than on conventional chemotherapy. The current chronoFLO schedule deserves prospective assessment as a safe and more effective first-line treatment option than conventional delivery for male patients.