Deanna Mitchell1,2, Genevieve Bergendahl1, William Ferguson3, William Roberts4, Timothy Higgins5, Takamaru Ashikaga6, Mike DeSarno6, Joel Kaplan7, Jacqueline Kraveka8, Don Eslin9, Alyssa Vander Werff1, Gina K Hanna10, Giselle L Saulnier Sholler1,2. 1. Helen DeVos Children's Hospital, Grand Rapids, Michigan. 2. Michigan State University College of Human Medicine, Grand Rapids, Michigan. 3. Cardinal Glennon Children's Medical Center, Saint Louis University School of Medicine, Saint Louis, Missouri. 4. Rady Children's Hospital, University of California San Diego School of Medicine, San Diego, California. 5. Department of Radiology, University of Vermont Medical Center, Burlington, Vermont. 6. Medical Biostatistics and Biometry Facility, University of Vermont College of Medicine, Burlington, Vermont. 7. Levine Children's Hospital, Charlotte, North Carolina. 8. Medical University of South Carolina, Charleston, South Carolina. 9. Arnold Palmer Hospital for Children, Orlando, Florida. 10. Dana-Farber Cancer Institute, Boston, Massachusetts.
Abstract
BACKGROUND: The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma. The secondary aims were to evaluate the pharmacokinetics of TPI 287 and the treatment responses. PROCEDURE: Eighteen patients were enrolled to a phase I dose escalation trial of weekly intravenous infusion of TPI 287 for two 28-day cycles with toxicity monitoring to determine the MTD, followed by two cycles of TPI 287 in combination with TMZ. Samples were collected to determine the pharmacokinetic parameters C(max), AUC(0-24), t(1/2), CL, and Vd on day 1 of cycles 1 (TPI 287 alone) and 3 (TPI 287 + TMZ) following TPI 287 infusion. Treatment response was evaluated by radiographic (CT or MRI) and radionuclide (MIBG) imaging for neuroblastoma. RESULTS: We determined the MTD of TPI 287 alone and in combination with temozolomide to be 125 mg/m(2). The non-dose-limiting toxicities at this dose were mainly anorexia and pain. The dose-limiting toxicities (DLTs) of two patients at 135 mg/m(2) were grade 3 hemorrhagic cystitis and grade 3 sensory neuropathy. CONCLUSIONS: Overall, TPI 287 was well tolerated by pediatric patients with refractory and relapsed neuroblastoma and medulloblastoma at a dose of 125 mg/m(2) IV on days 1, 8, and 15 of a 28 day cycle.
BACKGROUND: The primary aim of this Phase I study was to determine the maximum tolerated dose (MTD) of TPI 287 and the safety and tolerability of TPI 287 alone and in combination with temozolomide (TMZ) in pediatric patients with refractory or recurrent neuroblastoma or medulloblastoma. The secondary aims were to evaluate the pharmacokinetics of TPI 287 and the treatment responses. PROCEDURE: Eighteen patients were enrolled to a phase I dose escalation trial of weekly intravenous infusion of TPI 287 for two 28-day cycles with toxicity monitoring to determine the MTD, followed by two cycles of TPI 287 in combination with TMZ. Samples were collected to determine the pharmacokinetic parameters C(max), AUC(0-24), t(1/2), CL, and Vd on day 1 of cycles 1 (TPI 287 alone) and 3 (TPI 287 + TMZ) following TPI 287 infusion. Treatment response was evaluated by radiographic (CT or MRI) and radionuclide (MIBG) imaging for neuroblastoma. RESULTS: We determined the MTD of TPI 287 alone and in combination with temozolomide to be 125 mg/m(2). The non-dose-limiting toxicities at this dose were mainly anorexia and pain. The dose-limiting toxicities (DLTs) of two patients at 135 mg/m(2) were grade 3 hemorrhagic cystitis and grade 3 sensory neuropathy. CONCLUSIONS: Overall, TPI 287 was well tolerated by pediatric patients with refractory and relapsed neuroblastoma and medulloblastoma at a dose of 125 mg/m(2) IV on days 1, 8, and 15 of a 28 day cycle.
Authors: Cory T Zumbar; Aisulu Usubalieva; Paul D King; Xiaohui Li; Caroline S Mifsud; Hailey M Dalton; Muge Sak; Sara Urio; William M Bryant; Joseph P McElroy; George Farmer; Norman L Lehman Journal: J Neurooncol Date: 2018-02-02 Impact factor: 4.130
Authors: Jennifer L McQuade; Liberty P Posada; Srisuda Lecagoonporn; Suzanne Cain; Roland L Bassett; Sapna P Patel; Wen-Jen Hwu; Patrick Hwu; Michael A Davies; Agop Y Bedikian; Rodabe N Amaria Journal: Melanoma Res Date: 2016-12 Impact factor: 3.599
Authors: Richard M Tsai; Zachary Miller; Mary Koestler; Julio C Rojas; Peter A Ljubenkov; Howard J Rosen; Gil D Rabinovici; Anne M Fagan; Yann Cobigo; Jesse A Brown; Joo In Jung; Emma Hare; David S Geldmacher; Marissa Natelson-Love; Emily C McKinley; Phi N Luong; Emmeline L Chuu; Ryan Powers; Paige Mumford; Amy Wolf; Ping Wang; Merhdad Shamloo; Bruce L Miller; Erik D Roberson; Adam L Boxer Journal: JAMA Neurol Date: 2020-02-01 Impact factor: 18.302
Authors: Giselle L Saulnier Sholler; Eugene W Gerner; Genevieve Bergendahl; Robert B MacArthur; Alyssa VanderWerff; Takamaru Ashikaga; Jeffrey P Bond; William Ferguson; William Roberts; Randal K Wada; Don Eslin; Jacqueline M Kraveka; Joel Kaplan; Deanna Mitchell; Nehal S Parikh; Kathleen Neville; Leonard Sender; Timothy Higgins; Masao Kawakita; Kyoko Hiramatsu; Shun-Suke Moriya; André S Bachmann Journal: PLoS One Date: 2015-05-27 Impact factor: 3.240