更新于：2024-11-01

ALK-Positive Inflammatory Myofibroblastic Tumor

ALK阳性炎性肌纤维母细胞瘤

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 ALK阳性炎性肌纤维母细胞瘤相关的药物

Crizotinib

克唑替尼

靶点

ALK x EML4-ALK x MST1R x c-Met

作用机制

ALK抑制剂 [+3]

在研机构

Pfizer Europe MA EEIG [+3]

原研机构

Pfizer Global Manufacturing China

在研适应症

ALK阳性炎性肌纤维母细胞瘤 [+16]

非在研适应症

晚期癌症 [+25]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2011-08-26

100 项与 ALK阳性炎性肌纤维母细胞瘤相关的临床结果

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100 项与 ALK阳性炎性肌纤维母细胞瘤相关的转化医学

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0 项与 ALK阳性炎性肌纤维母细胞瘤相关的专利（医药）

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项与 ALK阳性炎性肌纤维母细胞瘤相关的文献（医药）

2024-09-01·Pediatric Blood & Cancer

Population modeling analyses of crizotinib in pediatric patients with ALK‐positive advanced cancers

Article

作者: Jerry, Li ; Swan, Lin ; Dana, Nickens ; Huiping, Xu ; Greengard, Emily ; Balis, Frank M.

AbstractBackgroundAlterations in the ALK (anaplastic lymphoma kinase) gene play a critical role in pathogenesis of anaplastic large cell lymphoma (ALCL). Crizotinib is a small molecule competitive inhibitor of ALK, ROS1, and MET kinases and was approved for pediatric patients with ALK‐positive relapsed or refractory, systemic ALCL, and ALK‐positive unresectable, recurrent, or refractory inflammatory myofibroblastic tumors (IMT).ProcedureCrizotinib data from pediatric patients with relapsed or refractory solid tumors, IMT, or ALCL were included in the analyses. All patients received crizotinib orally at doses ranging from 100 to 365 mg/m2 twice daily (BID). PopPK analyses were conducted to characterize crizotinib disposition in pediatric patients. Exposure–response (ER) safety and antitumor analyses were conducted to characterize relationships between crizotinib dose or exposure with safety and antitumor activity endpoints of interest.ResultsThe population pharmacokinetic (popPK), ER safety, and ER antitumor analysis included 98, 110, and 36 pediatric patients, respectively. A one‐compartment pharmacokinetic model with allometric scaling, first‐order elimination, and first‐order absorption with lag time adequately described the data. Natural log‐transformed model‐predicted crizotinib AUCss (steady‐state area under the concentration–time curve) demonstrated a significant, positive relationship with Grade ≥3 NEUTROPENIA and Any Grade VISION DISORDER. Crizotinib dose demonstrated a positive relationship with objective response rate.ConclusionsNo significant differences in PK were identified across a wide range of ages or across tumor types, suggesting body surface area (BSA)‐based dosing adequately adjusted for differences in patient size to achieve similar systemic crizotinib exposures across young children and adolescent pediatric patients. None of the myelosuppressive events except Grade ≥3 NEUTROPENIA had significant relationships identified with crizotinib dose or exposure, suggesting crizotinib is a tolerable treatment with less hematological toxicity than traditional chemotherapy regimens for pediatric patients with ALK‐mutated cancers. Results from the presented analyses support the pediatric dosing recommendations in the product label.

2024-06-01·Oncology and Therapy

Podcast on Emerging Treatment Options for Pediatric Patients with ALK-Positive Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic Tumors

Article

作者: Mossé, Yael P ; Lowe, Eric

Anaplastic large cell lymphoma (ALCL) and inflammatory myofibroblastic tumor (IMT) are rare cancers observed predominantly in children and young adults. ALCL accounts for 10-15% of all pediatric non-Hodgkin lymphomas and is commonly diagnosed at an advanced stage of disease. In children, 84-91% of cases of ALCL harbor an anaplastic lymphoma kinase (ALK) gene translocation. IMT is a rare mesenchymal neoplasm that also tends to occur in children and adolescents. Approximately 50-70% of IMT cases involve rearrangements in the ALK gene. A combination of chemotherapeutic drugs is typically used for children with ALK-positive ALCL, and the only known curative therapy for ALK-positive IMT is complete surgical resection. Crizotinib, a first-generation ALK inhibitor, was approved in the USA in 2021 for pediatric patients and young adults with relapsed or refractory ALK-positive ALCL; however, its safety and efficacy have not been established in older adults. In 2022, crizotinib was approved for adult and pediatric patients with unresectable, recurrent, or refractory ALK-positive IMT. This podcast provides an overview of ALK-positive ALCL and IMT. We discuss the current treatment landscape, the role of ALK tyrosine kinase inhibitors, and areas of future research.

2024-01-01·Asian Journal of Surgery

A case report of RRBP1-ALK fusion gene-positive epithelioid inflammatory myofibroblastic sarcoma with collagenous stroma and good prognosis

Letter

作者: Cheng, Na ; Xue, Liyan