PHY906联合卡培他滨联合治疗肝癌的Ⅱ期临床试验

StephenW

A Phase II Clinical Trial on the Combination Therapy of PHY906 Plus Capecitabine in Hepatocellular Carcinoma
Chun A Changou  1   2   3 , Her-Shyong Shiah  1 , Li-Tzong Chen  4 , Servina Liu  5 , Frank Luh  5 , Shwu-Huey Liu  6 , Yung-Chi Cheng  7 , Yun Yen  1
Affiliations
Affiliations

    1
    The PhD Program for Cancer Molecular Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan.
    2
    The PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
    3
    The Core Facility Center, Office of Research and Development, Taipei Medical University, Taipei, Taiwan.
    4
    National Health Research Institutes, Tainan, Taiwan.
    5
    Sino-American Cancer Foundation, Covina, California, USA.
    6
    Yiviva Inc., New York, New York, USA.
    7
    Yale University School of Medicine, New Haven, Connecticut, USA.

    PMID: 33140457 DOI: 10.1002/onco.13582

Abstract

Lessons learned: A PHY906 and capecitabine combination could be effective as a salvage therapy for patients with hepatocellular carcinoma (HCC) previously treated with multiple systemic therapies. This traditional Chinese medicine formulation can work with Western cancer chemotherapeutic agents to improve clinical outcomes or alleviate side effects for patients with advanced HCC.

Background: This study aimed to evaluate efficacy and safety of capecitabine combined with a PHY906 (a pharmaceutical-grade formulation of four traditional Chinese herbs) in the treatment of advanced hepatocellular carcinoma (HCC) in Asian patients who were positive for hepatitis B virus (HBV).

Methods: This study was an open-label, phase II safety and efficacy clinical trial of PHY906 and capecitabine in patients with advanced HCC. Patients received 750 mg/m2 capecitabine b.i.d. 14 days plus 800 mg of PHY906 b.i.d. on days 1-4 and days 8-11 every 21-day cycle. The primary endpoint was 6-month survival rate, and secondary endpoints were progression-free survival, overall survival, disease control rate, and safety.

Results: Thirty-nine subjects completed the study with a 46.2% stable disease rate. The median progression-free survival was 1.5 months, and median overall survival (mOS) was 6 months with a 51.3% 6-month survival rate. The most common adverse events included lower hemoglobin, diarrhea, pain, abdomen NOS, fatigue, increased AST, and bilirubin. Patients who (a) had not received previous chemotherapies or targeted therapy or (b) had lower starting alpha-fetoprotein (AFP) levels or (c) had HBV infection showed better clinical outcome.

Conclusion: Our data showed that PHY906 increases the therapeutic index of capecitabine by enhancing its antitumor activity and reduces its toxicity profile in advanced HCC.

Keywords: Capecitabine; Chinese herbal medicine; Hepatocellular carcinoma; PHY906.

StephenW

PHY906联合卡培他滨联合治疗肝癌的Ⅱ期临床试验
Chun A Changou 1 2 3，Shi-Shyong Shiah 1，Chen Li-Tzong 4，Servina Liu 5，Frank Luh 5，Liu Shhu-Huey Liu 6，Cheng Yung-Chi 7，Yun Yen 1
隶属关系
隶属关系

    1个
    台湾台北医科大学，癌症分子生物学和药物发现博士课程。
    2
    台北医科大学医学科技学院，转化医学博士课程，台湾台北。
    3
    台北医科大学研究与发展办公室核心设施中心，台湾台北。
    4
    台湾台南国立卫生研究院。
    5
    美国加利福尼亚州科维纳市的中美癌症基金会。
    6
    美国纽约，Yiviva公司。
    7
    耶鲁大学医学院，美国康涅狄格州纽黑文。

    PMID：33140457 DOI：10.1002 / onco.13582

抽象

经验教训：PHY906和卡培他滨组合可以有效地挽救先前接受过多种全身疗法的肝细胞癌（HCC）患者。这种中药制剂可与西方癌症化学治疗剂配合使用，以改善晚期HCC患者的临床疗效或减轻副作用。

背景：本研究旨在评估卡培他滨联合PHY906（四种中药的药物级制剂）在亚洲乙型肝炎病毒（HBV）阳性患者中治疗晚期肝细胞癌（HCC）的有效性和安全性）。

方法：这项研究是PHY906和卡培他滨治疗晚期HCC的开放性，II期安全性和有效性临床试验。患者接受750 mg / m2卡培他滨b.i.d. 14天加800毫克PHY906 b.i.d.每21天周期在1-4天和8-11天。主要终点为6个月生存率，次要终点为无进展生存率，总体生存率，疾病控制率和安全性。

结果：39名受试者完成了该研究，病死率为46.2％。中位无进展生存期为1.5个月，中位总体生存期（mOS）为6个月，6个月生存率为51.3％。最常见的不良事件包括血红蛋白降低，腹泻，疼痛，腹部NOS，疲劳，AST升高和胆红素升高。 （a）以前未接受过化学疗法或靶向治疗的患者，或（b）甲胎蛋白（AFP）起始水平较低，或（c）HBV感染的患者临床预后较好。

结论：我们的数据表明PHY906通过增强卡培他滨的抗肿瘤活性来提高卡培他滨的治疗指数，并降低其在晚期HCC中的毒性。

关键字：卡培他滨；中草药；肝细胞癌； PHY906。

StephenW

https://theoncologist.onlinelibr ... /10.1002/onco.13582