恩替诺特与卡培他滨联合治疗晚期乳腺癌的试点研究

IF 1.6 Q4 ONCOLOGY
International Journal of Breast Cancer Pub Date : 2024-02-07 eCollection Date: 2024-01-01 DOI:10.1155/2024/5515966
Trish Millard, Christiana Brenin, Clare Humphrey, Ajay Dhakal, Carla Falkson, Gina Petroni, Nolan A Wages, Patrick Dillon
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引用次数: 0

摘要

背景:乳腺癌在对高危疾病进行新辅助治疗后,如果发现任何残留疾病,其复发率都高得令人无法接受。临床数据表明表观遗传修饰药物对乳腺癌有辅助治疗作用,而临床前数据表明恩替诺司他与卡培他滨联用有协同作用,基于这些数据,我们对这些药物在转移性乳腺癌(MBC)中的应用进行了一项开放标签 I 期研究。这两种药物都已公布了用于联合治疗的剂量,但此前还未在人体试验中进行过联合应用:方法:两个学术中心开展了一项多点 I 期剂量递增研究。方法:在两个学术中心开展了一项多点 I 期剂量递增研究,入组患者均为接受过预处理、HER2 阴性 MBC 且病情可测量的患者。通过贝叶斯偏序持续评估法进行双剂量递增。剂量水平从恩替诺特 3 毫克到 5 毫克不等,卡培他滨 800 毫克/平方米到 1000 毫克/平方米不等:13名中性粒细胞白血病患者接受了四种剂量组合的治疗,中位数为4种既往疗法。最常见的毒性反应是中性粒细胞减少、血小板减少和掌跖感觉障碍,这些都是预料之中的毒性反应。没有观察到新的安全性信号。观察到一种剂量限制性毒性,但未超过 25% 的预设毒性率。中位治疗时间为 2.37 个月。未观察到部分或完全应答。由于药物供应限制,研究在进入扩展阶段之前提前结束:结论:恩替诺司他和卡培他滨的试验剂量组合对于重度预处理转移性乳腺癌可能是安全的。这项研究对恩替诺特治疗乳腺癌的临床研究已经停止,但这种药物在美国以外的药物开发仍在继续。对于根治性治疗后有高危残留癌的乳腺癌患者,仍然需要术后辅助药物治疗。该试验已在 NCT03473639 上注册。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A Pilot Study of the Combination of Entinostat with Capecitabine in Advanced Breast Cancer.

Background: Breast cancer has an unacceptably high recurrence rate when any residual disease is found following neoadjuvant treatment of high-risk disease. Based on clinical data suggesting an adjuvant role for epigenetic modifying agents in breast cancer and preclinical data suggesting synergistic activity of entinostat combined with capecitabine, we conducted a phase I, open-label study of these agents in metastatic breast cancer (MBC). Both agents have published doses for use in combination therapy, but the agents had not previously been combined with each other in a human trial.

Methods: A multisite phase I dose escalation study was performed at two academic centers. Patients with pretreated, HER2-negative MBC, and measurable disease were enrolled. Dual dose escalation was performed via a Bayesian partial order continual assessment method. Dose levels ranged from entinostat 3 mg to 5 mg and capecitabine 800 mg/m2 to 1000 mg/m2.

Results: Thirteen patients with MBC and a median of 4 lines of prior therapy were enrolled across four dose level combinations. The most common toxicities were neutropenia, thrombocytopenia, and palmar-plantar dysesthesia, which were expected toxicities. No new safety signals were observed. One dose-limiting toxicity was observed, which did not exceed a prespecified toxicity rate of 25%. The median treatment duration was 2.37 months. No partial nor complete responses were observed. The study was halted early prior to entering an expansion phase, due to drug supply limitations.

Conclusion: The tested dosing combinations of entinostat and capecitabine are likely safe in heavily pretreated metastatic breast cancer. This study's clinical investigation of entinostat in breast cancer was halted, but drug development of this agent continues outside the US. There remains a need for postoperative adjuvant drug therapy for the subpopulation of breast cancer patients with high-risk residual cancer after curative therapy. This trial is registered with NCT03473639.

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来源期刊
CiteScore
3.40
自引率
0.00%
发文量
25
审稿时长
19 weeks
期刊介绍: International Journal of Breast Cancer is a peer-reviewed, Open Access journal that provides a forum for scientists, clinicians, and health care professionals working in breast cancer research and management. The journal publishes original research articles, review articles, and clinical studies related to molecular pathology, genomics, genetic predisposition, screening and diagnosis, disease markers, drug sensitivity and resistance, as well as novel therapies, with a specific focus on molecular targeted agents and immune therapies.
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