Abramson Cancer Center, Philadelphia, Pennsylvania2Division of Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
Division of Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
JAMA Oncol. 2016 Feb;2(2):253-60. doi: 10.1001/jamaoncol.2015.4701.
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.
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.
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.
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.
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.
帕博西尼（PD0332991）是一种新开发的药物，因其在激素受体阳性、ERBB2 阴性（以前称为 HER2 或 HER2/neu）乳腺癌的一线转移性治疗中与内分泌治疗联合使用而获得突破性治疗认定和最近美国食品和药物管理局的批准。
本文描述了帕博西尼在广泛的肿瘤类型中的临床前和转化数据以及早期和晚期临床试验。我们讨论了药效学、药代动力学、毒性作用和临床反应率。
2015 年 3 月 1 日，我们对描述帕博西尼开发的文献进行了综述。我们使用了 PubMed 搜索词“PD0332991”、“palbociclib”和“CDK4/6 抑制剂”来查找所有感兴趣的已发表文章，没有对出版日期进行限制。
帕博西尼是一种有效的、特异性的口服细胞周期蛋白依赖性激酶（CDK）4/6 抑制剂，具有强有力的临床前数据支持其在视网膜母细胞瘤蛋白表达肿瘤中的活性。1 期临床试验证明了其安全性，2 期临床试验表明在套细胞淋巴瘤、乳腺癌、脂肪肉瘤和畸胎瘤中具有单药活性，主要毒性作用是可逆性中性粒细胞减少。帕博西尼与内分泌治疗联合应用可改善内分泌治疗初治和内分泌治疗耐药的转移性疾病的无进展生存期。
帕博西尼具有良好的耐受性，在多种癌症中具有治疗潜力，包括乳腺癌，其疗效已单独和与内分泌治疗联合证明。帕博西尼与内分泌治疗、化疗和靶向治疗的其他联合方案在各种肿瘤中具有潜力，目前正在进行 3 期临床试验。
