Phase I, Dose-Escalation Study of BKM120, an Oral Pan-Class I PI3K Inhibitor, in Patients With Advanced Solid Tumors
Top Cited Papers
- 20 January 2012
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 30 (3), 282-290
- https://doi.org/10.1200/jco.2011.36.1360
Abstract
Purpose This phase I dose-escalation study investigated the maximum-tolerated dose (MTD), safety, preliminary activity, pharmacokinetics (PK), and pharmacodynamics of BKM120, a potent and highly specific oral pan-Class I PI3K inhibitor. Patients and Methods Thirty-five patients with advanced solid tumors received daily BKM120 12.5 to 150 mg. Dose escalation was guided by a Bayesian logistic regression model with overdose control. Assessments included archival tumor molecular status, response by Response Evaluation Criteria in Solid Tumors (RECIST), positron emission tomography tracer uptake ([18F]fluorodeoxyglucose positron emission tomography [FDG-PET]), fasting plasma C-peptide, and phosphorylated ribosomal protein S6 (pS6) in skin biopsies. Results Overall, treatment was well tolerated. Dose-limiting toxicities were grade 2 mood alteration (80 mg), grade 3 epigastralgia, grade 3 rash, grade 2 and grade 3 mood alteration (100 mg), and two grade 4 hyperglycemia (150 mg). The MTD was 100 mg/d. Frequent tr...Keywords
This publication has 36 references indexed in Scilit:
- The PI3K Pathway As Drug Target in Human CancerJournal of Clinical Oncology, 2010
- PIK3CA Mutation in Colorectal Cancer: Relationship with Genetic and Epigenetic AlterationsNeoplasia, 2008
- The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolismNature Reviews Genetics, 2006
- Oncogenic PI3K deregulates transcription and translationNature Reviews Cancer, 2005
- Frequent Mutation of the PIK3CA Gene in Ovarian and Breast CancersClinical Cancer Research, 2005
- PIK3CA gene is frequently mutated in breast carcinomas and hepatocellular carcinomasOncogene, 2004
- The Phosphoinositide 3-Kinase PathwayScience, 2002
- Cellular Function of Phosphoinositide 3-Kinases: Implications for Development, Immunity, Homeostasis, and CancerAnnual Review of Cell and Developmental Biology, 2001
- Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expressionProceedings of the National Academy of Sciences of the United States of America, 1998
- PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate CancerScience, 1997