abemaciclib联合阿比特龙治疗转移性去势抵抗性前列腺癌的1期临床研究

IF 1.8 4区医学 Q3 INFECTIOUS DISEASES

Journal of Chemotherapy Pub Date : 2025-09-09 DOI:10.1080/1120009X.2025.2551397

Nobuaki Matsubara, Koji Dozono, Karim Nacerddine, Kaijiro Maeda

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引用次数: 0

摘要

这项1期、多中心、开放标签研究的目的是评估abemaciclib在日本转移性阉割抵抗性前列腺癌（mCRPC）患者中的安全性、耐受性和药代动力学（PK），该药物的全球推荐2期剂量（RP2D）为200mg，每日两次，联合标准剂量的阿比特龙和泼尼松龙。首次给药后28天评估剂量限制性毒性（dlt）。6名患者接受了治疗，所有患者均经历了至少一次治疗引起的不良事件（TEAE），大多数为低度；未发生4级或5级teae。腹泻是最常见的TEAE（除1例2级外，所有事件均为1级）。3例患者出现严重不良事件（SAEs），其中2例导致停药。PK谱与非日本患者一致，未检测到PK -药物相互作用。该研究证实，abemaciclib的全球RP2D适用于接受阿比特龙和泼尼松龙治疗的日本mCRPC患者。

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A Phase 1 study of abemaciclib plus abiraterone in Japanese patients with metastatic castration-resistant prostate cancer.

The aim of this Phase 1, multicentre, open-label study was to evaluate the safety, tolerability and pharmacokinetics (PK) of abemaciclib administered at global recommended Phase 2 dose (RP2D) of 200 mg twice daily, combined with standard doses of abiraterone and prednisolone, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Dose-limiting toxicities (DLTs) were assessed for 28 days post-first dose. Six patients were treated, and all experienced at least one treatment-emergent adverse event (TEAE), mostly low grade; no Grade 4 or 5 TEAEs occurred. Diarrhoea was the most common TEAE (all events were Grade 1 except for one Grade 2). Three patients experienced serious adverse events (SAEs), leading to treatment discontinuation in two cases. The PK profile was consistent with non-Japanese patients, with no PK drug-drug interactions detected. The study confirms that the global RP2D of abemaciclib is suitable for Japanese patients with mCRPC treated with abiraterone and prednisolone.

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来源期刊

Journal of Chemotherapy 医学-药学

CiteScore

3.70

自引率

0.00%

发文量

144

审稿时长

6-12 weeks

期刊介绍： The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy. The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs. Specific areas of focus include, but are not limited to: · Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents; · Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy; · Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents; · The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs; · Drug interactions in single or combined applications; · Drug resistance to antimicrobial and anticancer drugs; · Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research; · Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs; · Pharmacogenetics and pharmacogenomics; · Precision medicine in infectious disease therapy and in cancer therapy; · Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.