Filipa Lynce1,2, Hongkun Wang3, Emanuel F Petricoin4, Paula R Pohlmann1,2, Brandon Smaglo5, Jimmy Hwang6, Aiwu R He1,2, Deepa S Subramaniam1,2,7, John Deeken8, John Marshall1,2, Michael J Pishvaian9,10. 1. Lombardi Comprehensive Cancer Center, 3800 Reservoir Road NW, Washington, DC, 20007, USA. 2. Georgetown University Medical Center, Washington, DC, USA. 3. Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University, Washington, DC, USA. 4. Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA. 5. Department of Medicine, Baylor College of Medicine, Houston, TX, USA. 6. Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA. 7. AstraZeneca plc, Gaithersburg, Maryland, USA. 8. Inova Schar Cancer Institute, Inova Health System, Falls Church, Fairfax, VA, USA. 9. Lombardi Comprehensive Cancer Center, 3800 Reservoir Road NW, Washington, DC, 20007, USA. pishvaim@georgetown.edu. 10. Georgetown University Medical Center, Washington, DC, USA. pishvaim@georgetown.edu.
Abstract
PURPOSE: This phase I trial evaluated the maximum tolerated dose, safety and preliminary efficacy of lapatinib, a HER1, HER2 dual kinase inhibitor plus bortezomib, a proteasome inhibitor, in adult patients with advanced malignancies. METHODS: Patients were enrolled in a standard 3 + 3 design with lapatinib (L) 750, 1000, 1250 or 1500 mg daily, and bortezomib (B) 0.7, 1.0, 1.3 or 1.6 mg/m2 for 3 weeks with 1 week off. Dose-limiting toxicities (DLT) were assessed during the first 28 days RESULTS: Fifteen patients received the combination of lapatinib and bortezomib in three different cohorts and ten were evaluable for DLT. There were no DLTs. Anorexia was the most common adverse event. Biomarker analysis showed upregulation of p27 expression with lapatinib and the combination. No tumor response was observed and thus the study was closed early. CONCLUSION: The combination of lapatinib and bortezomib was well tolerated but no complete or partial tumor responses were observed at the dose levels tested. CLINICALTRIALS. GOV IDENTIFIER: NCT01497626.
PURPOSE: This phase I trial evaluated the maximum tolerated dose, safety and preliminary efficacy of lapatinib, a HER1, HER2 dual kinase inhibitor plus bortezomib, a proteasome inhibitor, in adult patients with advanced malignancies. METHODS:Patients were enrolled in a standard 3 + 3 design with lapatinib (L) 750, 1000, 1250 or 1500 mg daily, and bortezomib (B) 0.7, 1.0, 1.3 or 1.6 mg/m2 for 3 weeks with 1 week off. Dose-limiting toxicities (DLT) were assessed during the first 28 days RESULTS: Fifteen patients received the combination of lapatinib and bortezomib in three different cohorts and ten were evaluable for DLT. There were no DLTs. Anorexia was the most common adverse event. Biomarker analysis showed upregulation of p27 expression with lapatinib and the combination. No tumor response was observed and thus the study was closed early. CONCLUSION: The combination of lapatinib and bortezomib was well tolerated but no complete or partial tumor responses were observed at the dose levels tested. CLINICALTRIALS. GOV IDENTIFIER: NCT01497626.
Authors: John F Deeken; Hongkun Wang; Deepa Subramaniam; Aiwu Ruth He; Jimmy Hwang; John L Marshall; Christina E Urso; Yiru Wang; Corinne Ramos; Kenneth Steadman; Michael J Pishvaian Journal: Cancer Date: 2015-01-29 Impact factor: 6.860
Authors: Said Akli; Xin-Qiao Zhang; Jolanta Bondaruk; Susan L Tucker; P Bogdan Czerniak; William F Benedict; Khandan Keyomarsi Journal: Cell Cycle Date: 2012-04-01 Impact factor: 4.534
Authors: Kari B Wisinski; Amye J Tevaarwerk; Mark E Burkard; Murtuza Rampurwala; Jens Eickhoff; Maria C Bell; Jill M Kolesar; Christopher Flynn; Glenn Liu Journal: Clin Cancer Res Date: 2016-03-29 Impact factor: 12.531
Authors: Claudius Mueller; Kirsten H Edmiston; Calvin Carpenter; Eoin Gaffney; Ciara Ryan; Ronan Ward; Susan White; Lorenzo Memeo; Cristina Colarossi; Emanuel F Petricoin; Lance A Liotta; Virginia Espina Journal: PLoS One Date: 2011-08-17 Impact factor: 3.240
Authors: David M Hyman; Anne A Eaton; Mrinal M Gounder; Erika G Pamer; Jasmine Pettiford; Richard D Carvajal; S Percy Ivy; Alexia Iasonos; David R Spriggs Journal: Oncotarget Date: 2015-08-07
Authors: Przemysław Duda; Shaw M Akula; Stephen L Abrams; Linda S Steelman; Alberto M Martelli; Lucio Cocco; Stefano Ratti; Saverio Candido; Massimo Libra; Giuseppe Montalto; Melchiorre Cervello; Agnieszka Gizak; Dariusz Rakus; James A McCubrey Journal: Cells Date: 2020-04-30 Impact factor: 6.600