Yi-Long Wu1, L I Zhang2, Lucia Trandafir3, Tuochuan Dong4, Vincent Duval5, Katharine Hazell5, Binghe Xu6. 1. Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, P.R. China. 2. Sun Yat-Sen University Cancer Center, Guangzhou, P.R. China. 3. Novartis Pharma S.A.S., Paris, France. 4. Novartis Pharmaceutical Corporation, East Hanover, NJ, U.S.A. 5. Novartis Pharma AG, Basel, Switzerland. 6. National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China xubinghe@medmail.com.cn.
Abstract
BACKGROUND/AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSION: 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. Copyright
BACKGROUND/AIM: The phosphatidylinositol-3-kinase (PI3K) signaling pathway is frequently activated in cancer. Buparlisib (BKM120), an oral pan-PI3K inhibitor, inhibits proliferation of humancancer 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. MATERIALS AND METHODS: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. RESULTS: 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%). CONCLUSION: 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. Copyright
Authors: U A Matulonis; G M Wulf; W T Barry; M Birrer; S N Westin; S Farooq; K M Bell-McGuinn; E Obermayer; C Whalen; T Spagnoletti; W Luo; H Liu; R C Hok; C Aghajanian; D B Solit; G B Mills; B S Taylor; H Won; M F Berger; S Palakurthi; J Liu; L C Cantley; E Winer Journal: Ann Oncol Date: 2017-03-01 Impact factor: 32.976
Authors: Nan Wu; Jinghua Zhang; Jing Zhao; Kun Mu; Jun Zhang; Zhao Jin; Jinpu Yu; Juntian Liu Journal: Oncol Lett Date: 2018-08-10 Impact factor: 2.967