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辅助糖皮质激素治疗卵巢癌的两面性。

The Two Faces of Adjuvant Glucocorticoid Treatment in Ovarian Cancer.

机构信息

Lunenfeld-Tanenbaum Research Institute at Sinai Health Systems, University of Toronto, Toronto, ON, Canada.

Division of Gynecological Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

出版信息

Horm Cancer. 2018 Apr;9(2):95-107. doi: 10.1007/s12672-017-0319-0. Epub 2018 Jan 8.

Abstract

Adjuvant glucocorticoid treatment is routinely used in the treatment of ovarian cancer to mitigate the undesirable side effects of chemotherapy, thereby enhancing tolerability to higher cytotoxic drug doses and frequency of treatment cycles. However, in vitro and preclinical in vivo and ex vivo studies indicate that glucocorticoids may spare tumor cells from undergoing cell death through enhanced cell adhesion, promotion of anti-inflammatory signaling, and/or inhibition of apoptotic pathways. The implications of laboratory studies showing potential negative impact on the efficacy of chemotherapy have been long overlooked since clinical investigations have found no apparent survival detriment attributable to adjuvant glucocorticoid use. Importantly, these clinical studies were not randomized and most did not consider glucocorticoid receptor status, a vital determinant of tumor response to glucocorticoid administration. Additionally, the clinically beneficial elements of increased chemotherapy treatment adherence and dosing afforded by adjuvant glucocorticoids may offset and therefore mask their anti-chemotherapy activities. This review summarizes the current evidence on the impact of glucocorticoids in ovarian cancer and discusses the need for further research and development of alternative strategies to ameliorate untoward side effects of chemotherapy.

摘要

辅助糖皮质激素治疗被常规用于卵巢癌的治疗中,以减轻化疗的不良副作用,从而提高对更高细胞毒性药物剂量和治疗周期频率的耐受性。然而,体外和临床前体内和离体研究表明,糖皮质激素可能通过增强细胞黏附、促进抗炎信号和/或抑制细胞凋亡途径来使肿瘤细胞免于死亡。由于临床研究并未发现辅助性糖皮质激素使用导致生存受损的明显迹象,因此长期以来,实验室研究显示对化疗疗效有潜在负面影响的结果一直被忽视。重要的是,这些临床研究并非随机进行,而且大多数研究都没有考虑糖皮质激素受体状态,这是肿瘤对糖皮质激素给药反应的一个重要决定因素。此外,辅助性糖皮质激素增加化疗治疗依从性和剂量的临床获益可能会抵消并掩盖其对化疗的拮抗作用。这篇综述总结了目前关于糖皮质激素对卵巢癌影响的证据,并讨论了进一步研究和开发替代策略以改善化疗不良副作用的必要性。

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