将细胞色素c过氧化碳酰胺化学疗法与先前常规治疗相结合，可在晚期三阴性乳腺癌患者中获得更好的总体生存率：对NCT03340935试验的一项副分析。
Adding fasting-mimicking diet to first-line carboplatin-based chemotherapy is associated with better overall survival in advanced triple-negative breast cancer patients: A subanalysis of the NCT03340935 trial.
发表日期：2023 Aug 24
作者：
Francesca Ligorio, Riccardo Lobefaro, Giovanni Fucà, Leonardo Provenzano, Lucrezia Zanenga, Vincenzo Nasca, Caterina Sposetti, Giulia Salvadori, Angela Ficchì, Andrea Franza, Antonia Martinetti, Elisa Sottotetti, Barbara Formisano, Catherine Depretto, Gianfranco Scaperrotta, Antonino Belfiore, Andrea Vingiani, Cristina Ferraris, Giancarlo Pruneri, Filippo de Braud, Claudio Vernieri
来源：
Disease Models & Mechanisms
摘要：
严重的热量限制，通过循环性禁食或模仿禁食饮食（FMD），增强了细胞毒性化疗对三阴乳腺癌（TNBC）小鼠模型的抗肿瘤活性。这种效应主要由禁食/FMD导致的血浆葡萄糖浓度降低和抗肿瘤免疫力提升介导。然而，关于循环FMD可能如何影响中晚期TNBC（aTNBC）患者的预后的临床证据尚缺乏。我们比较了接受NCT03340935试验中第一线卡铂-吉西他滨联合循环FMD的14例aTNBC患者的总生存期（OS）与接受单独使用卡铂化疗的连续76例aTNBC患者在Fondazione IRCCS Istituto Nazionale dei Tumori的OS。使用多变量Cox回归模型来调整FMD对其他预后变量的预后影响。与仅接受化疗的患者相比，接受循环FMD联合卡铂-吉西他滨的患者的OS较好（中位数OS 30.3个月，95% CI 18-NR，而17.2个月，95% CI 15.3-25.1，log-rank P值为.041）。多变量分析证实了FMD使用与较好OS之间的关联（HR：0.40；95% CI：0.19-0.86；P = .019），并且在根据患者ECOG PS和新发转移性疾病的存在进行倾向得分匹配后，这种关联得到了证实（HR：0.41；95% CI：0.21-0.83；P = .013）。循环FMD联合第一线化疗可能改善aTNBC患者的临床结果。我们的研究为进行II期试验铺平了道路，以研究循环FMD是否能够增强早期TNBC或aTNBC患者的化疗或化疗免疫疗法的抗肿瘤活性/疗效。© 2023 UICC.
Severe calorie restriction, in the form of cyclic fasting or fasting-mimicking diets (FMDs), boosts the antitumor activity of cytotoxic chemotherapy in mouse models of triple-negative breast cancer (TNBC). This effect is mostly mediated by fasting/FMD-induced reduction of plasma glucose concentration and by a boost in antitumor immunity. However, clinical evidence that cyclic FMD may impact on the outcomes of advanced TNBC (aTNBC) patients is lacking. We compared the overall survival (OS) of 14 aTNBC patients receiving first-line carboplatin-gemcitabine plus cyclic FMD in the context of the NCT03340935 trial with the OS of 76 consecutive aTNBC patients treated with carboplatin-based chemotherapy alone at Fondazione IRCCS Istituto Nazionale dei Tumori. Multivariable Cox regression models were used to adjust the prognostic impact of FMD for other prognostic variables. Patients undergoing cyclic FMD in combination with carboplatin-gemcitabine had better OS when compared to patients receiving chemotherapy alone (median OS 30.3 months, 95% CI 18-NR, vs 17.2 months, 95% CI 15.3-25.1, log-rank P value .041). Multivariable analysis confirmed an association between FMD use and better OS (HR: 0.40; 95% CI: 0.19-0.86; P = .019) also after propensity score-based matching according to patient ECOG PS and the presence of de novo metastatic disease (HR: 0.41; 95% CI: 0.21-0.83; P = .013). Cyclic FMD in combination with first-line chemotherapy may improve clinical outcomes in aTNBC patients. Our study paves the way for conducting phase II trials to investigate if cyclic FMD can increase the antitumor activity/efficacy of chemotherapy or chemoimmunotherapy in patients with early-stage TNBC or aTNBC.© 2023 UICC.