JAMA肿瘤学:乳腺癌新药多用,有望成为多种癌症“狙击手”
2015/12/31
近日,《JAMA Oncology》杂志上的一则研究表明新型口服药物Palbociclib不仅能有效抗击乳腺癌,与内分泌疗法等相结合还可对抗其他癌症。该结果由宾夕法尼亚大学艾布拉姆森癌症中心的研究人员将临床研究数据与已有的文献综述相结合而得出。


近日,《JAMA Oncology》杂志上的一则研究表明新型口服药物Palbociclib不仅能有效抗击乳腺癌,与内分泌疗法相结合还可对抗其他癌症。该结果由宾夕法尼亚大学艾布拉姆森癌症中心的研究人员将临床研究数据与已有的文献综述相结合而得出。

Palbociclib通过抑制CDK4和CDK6酶的活性来靶向肿瘤细胞,CDK4和CDK6酶可推动细胞分裂使癌细胞激增,Palbociclib也是首个获批的用于治疗乳腺癌的CDK4/6抑制剂。本文的主要作者艾布拉姆森癌症中心和宾夕法尼亚大学佩雷尔曼医学院的血液学/肿瘤学教授Amy S. Clark说,“所有的活细胞都进行细胞分裂,而Palbociclib具有独特的能力可阻止细胞分裂进程,因而它具有潜在的广泛实用性。将Palbociclib与其他抗癌疗法(如内分泌疗法、化疗、靶向治疗)相结合,可组成一个强大的可对抗其他癌症的疗法。”

本文资深作者艾布拉姆森癌症中心“肿瘤治疗发展项目”主任血液/肿瘤学教授Peter J. O'Dwyer表示,“这种药物除了对中性粒白细胞有轻微影响外,还对正常细胞有影响。在肿瘤中,它可引起肿瘤收缩或阻止生长。自从发现了这种药物对CDK4/6的新功效,我们会考虑将其与其他抗癌疗法相结合使之发挥更大的效用。”O'Dwyer补充道,“除了抑制细胞周期,Palbociclib被证明可改变CDK4/6的非细胞周期功能,这一发现有望扩大其的治疗范围。”

宾夕法尼亚大学研究团队通过分析130篇相关文献,并结合自己的研究结果,最终发现除了对特定类型乳腺癌的抵抗具有安全性和有效性之外,Palbociclib的早期试验证实了其对抗淋巴瘤、肉瘤、畸胎瘤以及其他罕见肿瘤也有效。在推荐的剂量范围内,宾夕法尼亚大学通过PET成像系统来验证该药物对肿瘤的效果。

在乳腺癌和其他癌症的临床试验中,Palbociclib已被证明每日一次给药是安全的。然而,Palbociclib也会引起一定的副作用,包括可逆性中粒细胞减少、中性粒细胞数量异常低。中性粒细胞是一种白细胞,可帮助抵抗感染,中性粒细胞数量越少,病人感染疾病的几率越大。在这种情况下,建议暂停使用该药物或减少药物用量;Palbociclib的其他副作用还包括疲劳、恶心、腹泻、便秘和皮疹。

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  • Palbociclib (PD0332991)—a Selective and Potent Cyclin-Dependent Kinase Inhibitor

    Importance Palbociclib (PD0332991) is a newly developed drug that received breakthrough designation and recent US Food and Drug Administration approval in combination with endocrine therapy in the treatment of hormone receptor positive, ERBB2-negative (formerly HER2 or HER2/neu) breast cancer in the first-line metastatic setting. Objective Herein we describe the preclinical and translational data and early- and late-phase clinical trials in which palbociclib has been investigated in a broad array of tumor types. We discuss the pharmacodynamics, pharmacokinetics, toxic effects, and clinical response rates. Evidence Review On March 1, 2015, we conducted a review of the literature describing the development of palbociclib. We used the PubMed search terms “PD0332991,” “palbociclib,” and “CDK4/6 inhibitor” to find all published articles of interest, without limitation as to publication date. Findings Palbociclib is a potent and specific oral cyclin-dependent kinase (CDK) 4/6 inhibitor that has strong preclinical data to support its activity in retinoblastoma protein–expressing tumors. Phase 1 trials have demonstrated safety, and phase 2 trials have shown single-agent activity in mantle-cell lymphoma, breast cancer, liposarcoma, and teratoma with reversible neutropenia as the main toxic effect. Addition of palbociclib to endocrine therapy improves progression-free survival in endocrine therapy–naïve and endocrine therapy–resistant metastatic settings. Conclusions and Relevance Palbociclib is well tolerated and has therapeutic potential for multiple cancers, including breast cancer, where its efficacy has been demonstrated alone and in combination with endocrine therapy. Additional combinations of palbociclib with endocrine therapy, chemotherapy, and targeted therapy have potential in various tumors, and phase 3 trials are under way.

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