title: Alectinib Dose Escalation Reinduces Central Nervous System Responses in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Relapsing on Standard Dose Alectinib.
abstract: The central nervous system (CNS) is an important and increasingly recognized site of treatment failure in anaplastic lymphoma kinase (ALK)-positive, non-small cell lung cancer (NSCLC) patients receiving ALK inhibitors. In this report, we describe two ALK-positive patients who experienced initial improvements in CNS metastases on standard dose alectinib (600 mg twice daily), but who subsequently experienced recurrences with symptomatic leptomeningeal metastases. Both patients were dose-escalated to alectinib 900 mg twice daily, resulting in repeat clinical and radiographic responses. Our results suggest that dose intensification of alectinib may be necessary to overcome incomplete ALK inhibition in the CNS and prolong the durability of responses in patients with CNS metastases, particularly those with leptomeningeal carcinomatosis.
authors: Department of Medicine, Massachusetts General Hospital, Boston, MA. Electronic address: jgainor@partners.org.
authors: Justin F
authors: JF
authors: Gainor
authors: Department of Neurology, Massachusetts General Hospital, Boston, MA.
authors: Andrew S
authors: AS
authors: Chi
authors: Department of Medicine, Massachusetts General Hospital, Boston, MA.
authors: Jennifer
authors: J
authors: Logan
authors: Department of Radiology, Massachusetts General Hospital, Boston, MA.
authors: Ranliang
authors: R
authors: Hu
authors: Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA.
authors: Kevin S
authors: KS
authors: Oh
authors: Department of Medicine, Massachusetts General Hospital, Boston, MA.
authors: Priscilla K
authors: PK
authors: Brastianos
authors: Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA.
authors: Helen A
authors: HA
authors: Shih
authors: Department of Medicine, Massachusetts General Hospital, Boston, MA.
authors: Alice T
authors: AT
authors: Shaw
mesh_terms: D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D001932:Brain Neoplasms / Q000188:drug therapy / Q000556:secondary*; D002227:Carbazoles / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors*
chemical_list: D002227:Carbazoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C582670:alectinib
keywords: ALK; Alectinib; Anaplastic lymphoma kinase; Leptomeningeal metastases