TY - JOUR
T1 - A Phase 1 Trial of TPI 287 as a Single Agent and in Combination With Temozolomide in Patients with Refractory or Recurrent Neuroblastoma or Medulloblastoma
AU - Mitchell, Deanna
AU - Bergendahl, Genevieve
AU - Ferguson, William
AU - Roberts, William
AU - Higgins, Timothy
AU - Ashikaga, Takamaru
AU - Desarno, Mike
AU - Kaplan, Joel
AU - Kraveka, Jacqueline
AU - Eslin, Don
AU - Werff, Alyssa Vander
AU - Hanna, Gina K.
AU - Sholler, Giselle L.Saulnier
N1 - Publisher Copyright:
© 2015 Wiley Periodicals, Inc.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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 Cmax, AUC0-24, t1/2, 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/m2. The non-dose-limiting toxicities at this dose were mainly anorexia and pain. The dose-limiting toxicities (DLTs) of two patients at 135 mg/m2 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/m2 IV on days 1, 8, and 15 of a 28 day cycle.
AB - 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 Cmax, AUC0-24, t1/2, 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/m2. The non-dose-limiting toxicities at this dose were mainly anorexia and pain. The dose-limiting toxicities (DLTs) of two patients at 135 mg/m2 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/m2 IV on days 1, 8, and 15 of a 28 day cycle.
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U2 - 10.1002/pbc.25687
DO - 10.1002/pbc.25687
M3 - Article
C2 - 26235333
AN - SCOPUS:84951568617
SN - 1545-5009
VL - 63
SP - 39
EP - 46
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 1
ER -