title: Phase I Study of the Pan-PI3K Inhibitor Buparlisib in Adult Chinese Patients with Advanced Solid Tumors.
abstract: The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in cancer. Buparlisib (BKM120), an oral pan-PI3K inhibitor, inhibits proliferation of human cancer in preclinical models. Studies of buparlisib in Western and Japanese adults with advanced solid tumors established a recommended dose of 100 mg/day and showed an acceptable safety profile and evidence of efficacy. This phase I dose-escalation/expansion study aimed to establish the maximum tolerated dose (MTD) of single-agent, once daily oral buparlisib in Chinese patients with advanced solid tumors.
  
  
  
  Patients (n=32; primary tumor site: lung (n=15), breast (n=10) or head and neck (n=7); ≥2 prior lines of antineoplastic therapy (n=26)) received 80 mg (n=15) or 100 mg (n=17) daily buparlisib.
  
  
  
  Five patients experienced dose-limiting toxicities: grade (G)3 depression (n=1), G2 hyperglycemia (n=3) and G3 hyperglycemia (n=1). Most frequent buparlisib-related adverse events were hyperglycemia (n=18; 56%), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increase (n=9; 28%), as well as anxiety (n=6; 19%); most common buparlisib-related G3/4 adverse events: hyperglycemia (n=3; 9%), ALT and AST increase (n=2; 6%), as well as gamma-glutamyltransferase increase (n=2; 6%). Best response was stable disease (SD) in 10 patients (31%).
  
  
  
  The MTD of buparlisib was declared as 100 mg/day. Safety, efficacy and pharmacokinetic data from this study were similar to those previously reported in Western and Japanese populations.
authors: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, P.R. China.
authors: Yi-Long
authors: YL
authors: Wu
authors: Sun Yat-Sen University Cancer Center, Guangzhou, P.R. China.
authors: L I
authors: LI
authors: Zhang
authors: Novartis Pharma S.A.S., Paris, France.
authors: Lucia
authors: L
authors: Trandafir
authors: Novartis Pharmaceutical Corporation, East Hanover, NJ, U.S.A.
authors: Tuochuan
authors: T
authors: Dong
authors: Novartis Pharma AG, Basel, Switzerland.
authors: Vincent
authors: V
authors: Duval
authors: Novartis Pharma AG, Basel, Switzerland.
authors: Katharine
authors: K
authors: Hazell
authors: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China xubinghe@medmail.com.cn.
authors: Binghe
authors: B
authors: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002681:China; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D000081082:Phosphoinositide-3 Kinase Inhibitors
chemical_list: D000631:Aminopyridines; D000970:Antineoplastic Agents; D009025:Morpholines; C571178:NVP-BKM120; D000081082:Phosphoinositide-3 Kinase Inhibitors
keywords: Buparlisib; breast cancer; head and neck cancer; lung cancer; phosphatidylinositol-3-kinase