Safety and efficacy results from the first-in-human study of the oral MEK 1/2 inhibitor GSK1120212

Autor:	Donna S. Cox, Wells A. Messersmith, Leslie A. Fecher, H. A. Burris, Sujatha Nallapareddy, Keith T. Flaherty, J. R. Infante, Douglas J Demarini, Shannon R. Morris, Michael S. Gordon
Rok vydání:	2010
Předmět:	Cancer Research medicine.medical_specialty business.industry Melanoma Pharmacology medicine.disease Rash Gastroenterology Lymphoma Diarrhea Oncology Pharmacokinetics Internal medicine Pancreatic cancer Pharmacodynamics medicine medicine.symptom Adverse effect business
Zdroj:	Journal of Clinical Oncology. 28:2503-2503
ISSN:	1527-7755 0732-183X
Popis:	2503 Background: GSK1120212 is a potent and selective allosteric inhibitor of MEK1/2. The objectives of this study are to define the maximum tolerated dose (MTD), and to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and response rate of GSK1120212 in advanced solid tumors and lymphoma. Methods: GSK1120212 is given orally, once daily (QD). This is a three-part study:Part 1, dose-escalation; Part 2, expansion in selected tumor types to evaluate recommended phase II doses (RP2D); Part 3, PK-PD assessment using tumor biopsies or FDG-PET. Results: 84 patients (pts) have received ≥ 1 dose of GSK1120212, including 29 melanoma and 15 pancreatic cancer pts. The MTD is 3 mg QD and the current RP2D is 2 mg QD. Dose-limiting toxicities are rash (N=2), diarrhea (N=1), central serous retinopathy (N=2) and are reversible. At doses ≥ RP2D (N=77), the most common adverse events are rash (77%; 42% G1, 30% G2, 5% G3) and diarrhea (45%; 34% G1, 9% G2, 3% G3). GSK1120212 has a small peak: trough ratio of ∼ 2 and ...
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::102b14db77fc985f21c8d75a374181b7 https://doi.org/10.1200/jco.2010.28.15_suppl.2503 Zobrazit plný text záznamu