Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis.
Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis.
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DOI：
10.1038/srep45703
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发表时间：
2017-04-05
影响因子：
4.6
通讯作者：
Scartozzi M
中科院分区：
文献类型：
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作者：
Giampieri R;Prete MD;Prochilo T;Puzzoni M;Pusceddu V;Pani F;Maccaroni E;Mascia R;Baleani MG;Meletani T;Berardi R;Lanzillo AM;Mariotti S;Zaniboni A;Cascinu S;Scartozzi M
Regorafenib是一种口服多激酶抑制剂，用于治疗经过大量治疗的转移性结直肠癌患者，表现良好，尽管在第一次放射学评估中，只有不到50%的患者实现了疾病稳定或更好。除此之外，特别广泛的毒副作用(在接受治疗的患者中有50%的患者经历了G3或更多的NCI CTCAE)导致重新考虑在大多数患者中广泛使用它。我们回顾收集了在瑞格非尼单一治疗的前8周中所经历的非靶点效应的大小的数据，并分析了它们与总体存活率、无进展存活率和疾病控制率的相关性。多因素回归分析表明，皮疹(试验(B)：0.52，p = 0.0133)或甲状腺功能减退(试验(B)：0.11，p = 0.0349)与总生存率的改善显著相关。腹泻作为改善生存的预测因子在统计学上也有显著作用，但其独立的预后作用在多因素分析中丢失(Exp(B)：0.63，p = 0.162)。这是第一个显示这些形式的副作用的发生与瑞格拉非尼疗效之间存在潜在相关性的分析，然而，样本量的限制和我们分析的回溯性使我们无法得出明确的结论。
Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In addition to that a particularly broad spectrum of toxicities (experienced as G3 or more NCI CTCAE graded by 50% of patients treated) have led to reconsider its widespread use in the majority of patients. We retrospectively collected data about the magnitude of off-target effects experienced during the first 8-weeks of regorafenib monotherapy and analysed their correlation with overall survival, progression free survival and disease control rate. Our findings suggest that skin rash (Exp (B): 0.52, p = 0.0133) or hypothyroidism (Exp (B): 0.11, p = 0.0349) were significantly correlated with improved overall survival at multivariate regression analysis. It was also demonstrated a statistically significant role of diarrhea as predictor of improved survival but its independent prognostic role was lost at multivariate analysis (Exp (B): 0.63, p = 0.162). This is the first analysis showing a potential correlation between the onset of these forms of side effects and regorafenib efficacy, however sample size limitations and the retrospective nature of our analysis prevent us from drawing definitive conclusions.