文拉法辛在肿瘤学中的应用：支持治疗证据与新兴的临床前抗癌信号：一项系统综述。
完整摘要 · 中文译文
背景：文拉法辛是一种5-羟色胺-去甲肾上腺素再摄取抑制剂，已在肿瘤学领域针对若干支持治疗适应症进行研究，且近期还就其潜在抗癌活性进行了探讨。然而，现有证据分散于临床和临床前研究中。 目的：本系统综述旨在综合关于文拉法辛在肿瘤学中作用的现有证据，包括已确立的支持治疗应用和新兴的抗癌潜力。 方法：在PubMed、Scopus和Web of Science中进行了从数据库建库至2026年8月22日的系统文献检索。评估文拉法辛在癌症人群或实验性癌症模型中作用的原始临床和临床前研究符合纳入条件。临床和临床前证据分别采用叙述性方法进行综合。方法学质量分别采用Joanna Briggs研究所工具（用于临床研究）和SYRCLE偏倚风险工具（用于动物研究）进行评估。 结果：共纳入25项研究，包括23项临床研究和2项临床前研究。最强的临床证据支持文拉法辛用于治疗相关潮热，尤其是在接受内分泌治疗的乳腺癌幸存者中，最强的随机、安慰剂对照试验证据显示文拉法辛的减少幅度显著大于安慰剂（较高剂量P < 0.0001）；组内百分比降低也有报告，但不应将其解释为治疗效果。关于化疗所致周围神经病变的证据不一致 对急性奥沙利铂相关神经毒性可能有益，但对慢性CIPN的预防或常规治疗支持不足。其他支持治疗结局的证据有限，包括口腔黏膜炎相关疼痛、疲乏、睡眠质量、抑郁症状和生活质量。文拉法辛总体耐受性良好，尽管不良反应因剂量和对照药而异。临床前研究考察了抗癌活性，但结果并不等同：一项黑色素瘤模型研究显示文拉法辛通过JNK1/2-Nur77信号通路发挥直接抗增殖/促凋亡作用，而一项结直肠癌研究仅显示其对去甲肾上腺素驱动的肿瘤进展具有情境依赖性拮抗作用，文拉法辛单药无显著效应。目前尚无临床证据支持文拉法辛作为直接抗癌治疗。 结论：文拉法辛在支持治疗肿瘤学中对治疗相关潮热具有已确立的循证地位，而其在中性粒细胞减少性发热及CIPN和其他支持治疗适应证中的作用仍不确定。新出现的抗癌研究结果仅限于临床前模型，应视为产生假设性的。支持治疗适应证需要进一步随机临床试验，而在文拉法辛可考虑作为抗癌治疗进行临床评价之前，需要额外的机制和临床前验证。
完整摘要 · 英文原文
BACKGROUND: Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, has been investigated in oncology for several supportive care indications and, more recently, for potential anticancer activity. However, the available evidence remains fragmented across clinical and preclinical studies. OBJECTIVE: This systematic review aimed to synthesize the available evidence regarding the role of venlafaxine in oncology, including established supportive care applications and emerging anticancer potential. METHODS: A systematic literature search was conducted in PubMed, Scopus, and Web of Science from database inception to 22 August 2026. Original clinical and preclinical studies evaluating venlafaxine in cancer populations or experimental cancer models were eligible. Clinical and preclinical evidence was synthesized separately using a narrative approach. Methodological quality was assessed using Joanna Briggs Institute tools for clinical studies and the SYRCLE Risk of Bias tool for animal studies. RESULTS: 25 studies were included, comprising 23 clinical studies and 2 preclinical studies. The strongest clinical evidence supported venlafaxine for treatment-related hot flashes, particularly among breast cancer survivors receiving endocrine therapy, with the strongest randomized, placebo-controlled trial evidence showing significantly greater reductions with venlafaxine than placebo (P < 0.0001 for higher doses); within-group percentage reductions are also reported but should not be interpreted as treatment effects. Evidence for chemotherapy-induced peripheral neuropathy was inconsistent, with potential benefit for acute oxaliplatin-related neurotoxicity but insufficient support for prevention or routine treatment of chronic CIPN. Evidence for other supportive care outcomes, including oral mucositis-associated pain, fatigue, sleep quality, depressive symptoms, and quality of life, was limited. Venlafaxine was generally well tolerated, although adverse effects varied by dose and comparator. Preclinical studies investigated anticancer activity, but not equivalently: one in melanoma models showed direct antiproliferative/pro-apoptotic effects of venlafaxine via JNK1/2-Nur77 signaling, whereas a colorectal cancer study showed only context-dependent antagonism of norepinephrine-driven tumor progression, with no significant effect of venlafaxine alone. No clinical evidence currently supports venlafaxine as a direct anticancer treatment. CONCLUSION: Venlafaxine has an established evidence-based role in supportive oncology for treatment-related hot flashes, whereas its role in CIPN and other supportive care indications remains uncertain. Emerging anticancer findings are limited to preclinical models and should be considered hypothesis-generating. Further randomized clinical trials are needed for supportive care indications, while additional mechanistic and preclinical validation is required before venlafaxine can be considered for clinical evaluation as an anticancer therapy.