A Phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/ primitive neuroectodermal tumor, or brainstem glioma: A children's oncology group study

Maryam Fouladi, H. Stacy Nicholson, Tianni Zhou, Fred Laningham, Kathleen J. Helton, Emi Holmes, Kenneth Cohen, Rose Anne Speights, John Wright, Ian F. Pollack

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. An open-label Phase II study of tipifarnib was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), high-grade glioma (HGG), and diffuse intrinsic brainstem glioma (BSG). METHODS. Between January 2004 and July 2005, patients were enrolled and stratified as follows: Stratum 1, recurrent or refractory MB/PNET; Stratum 2, recurrent or refractory HGG; and Stratum 3, recurrent or refractory BSG. Patients received tipifarnib 200 mg/m2 per dose twice daily for 21 days repeated every 28 days. Patients who received enzyme-inducing anticonvulsants and other CYP3A4/5 inducers or inhibitors were excluded. The primary objective was to estimate the sustained response rate in all strata. RESULTS. Ninety-seven patients with a median age of 11.2 years (range, 3.2-21.9 years) were enrolled on the study, and 81 patients were evaluable for response. One of 35 patients with BSG and 1 of 31 patients with HGG had a sustained partial response. No responses were observed in 15 patients with MB/PNET. Eight patients (3 HGG, 1 MB, and 4 BSG) remained stable for ≥4 courses (range, 4-25 courses). The median number of courses received was 2 (range, 1-25 courses). The most frequent grade 3 and 4 toxicities included neutropenia (18.7%), thrombocytopenia (14.3%), and leukopenia (14.3%). The 6-month progression-free survival rate (±standard deviation) was 14% ± 6% for HGG, 6% ± 6% for MB/PNET and 3% ± 3% for BSG. CONCLUSIONS. Tipifarnib tolerated well but had little activity as a single agent in children with recurrent central nervous system malignancies.

Original languageEnglish (US)
Pages (from-to)2535-2541
Number of pages7
JournalCancer
Volume110
Issue number11
DOIs
StatePublished - Dec 1 2007

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tipifarnib
Primitive Neuroectodermal Tumors
Medulloblastoma
Transferases
Glioma
Brain Stem
Leukopenia
Neutropenia
Thrombocytopenia
Anticonvulsants
Disease-Free Survival

Keywords

  • Farnesyl transferase inhibitor
  • Phase II trial
  • Recurrent central nervous system malignancies
  • Tipifarnib

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A Phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/ primitive neuroectodermal tumor, or brainstem glioma : A children's oncology group study. / Fouladi, Maryam; Nicholson, H. Stacy; Zhou, Tianni; Laningham, Fred; Helton, Kathleen J.; Holmes, Emi; Cohen, Kenneth; Speights, Rose Anne; Wright, John; Pollack, Ian F.

In: Cancer, Vol. 110, No. 11, 01.12.2007, p. 2535-2541.

Research output: Contribution to journalArticle

Fouladi, Maryam ; Nicholson, H. Stacy ; Zhou, Tianni ; Laningham, Fred ; Helton, Kathleen J. ; Holmes, Emi ; Cohen, Kenneth ; Speights, Rose Anne ; Wright, John ; Pollack, Ian F. / A Phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/ primitive neuroectodermal tumor, or brainstem glioma : A children's oncology group study. In: Cancer. 2007 ; Vol. 110, No. 11. pp. 2535-2541.
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abstract = "BACKGROUND. An open-label Phase II study of tipifarnib was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), high-grade glioma (HGG), and diffuse intrinsic brainstem glioma (BSG). METHODS. Between January 2004 and July 2005, patients were enrolled and stratified as follows: Stratum 1, recurrent or refractory MB/PNET; Stratum 2, recurrent or refractory HGG; and Stratum 3, recurrent or refractory BSG. Patients received tipifarnib 200 mg/m2 per dose twice daily for 21 days repeated every 28 days. Patients who received enzyme-inducing anticonvulsants and other CYP3A4/5 inducers or inhibitors were excluded. The primary objective was to estimate the sustained response rate in all strata. RESULTS. Ninety-seven patients with a median age of 11.2 years (range, 3.2-21.9 years) were enrolled on the study, and 81 patients were evaluable for response. One of 35 patients with BSG and 1 of 31 patients with HGG had a sustained partial response. No responses were observed in 15 patients with MB/PNET. Eight patients (3 HGG, 1 MB, and 4 BSG) remained stable for ≥4 courses (range, 4-25 courses). The median number of courses received was 2 (range, 1-25 courses). The most frequent grade 3 and 4 toxicities included neutropenia (18.7{\%}), thrombocytopenia (14.3{\%}), and leukopenia (14.3{\%}). The 6-month progression-free survival rate (±standard deviation) was 14{\%} ± 6{\%} for HGG, 6{\%} ± 6{\%} for MB/PNET and 3{\%} ± 3{\%} for BSG. CONCLUSIONS. Tipifarnib tolerated well but had little activity as a single agent in children with recurrent central nervous system malignancies.",
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T1 - A Phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/ primitive neuroectodermal tumor, or brainstem glioma

T2 - A children's oncology group study

AU - Fouladi, Maryam

AU - Nicholson, H. Stacy

AU - Zhou, Tianni

AU - Laningham, Fred

AU - Helton, Kathleen J.

AU - Holmes, Emi

AU - Cohen, Kenneth

AU - Speights, Rose Anne

AU - Wright, John

AU - Pollack, Ian F.

PY - 2007/12/1

Y1 - 2007/12/1

N2 - BACKGROUND. An open-label Phase II study of tipifarnib was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), high-grade glioma (HGG), and diffuse intrinsic brainstem glioma (BSG). METHODS. Between January 2004 and July 2005, patients were enrolled and stratified as follows: Stratum 1, recurrent or refractory MB/PNET; Stratum 2, recurrent or refractory HGG; and Stratum 3, recurrent or refractory BSG. Patients received tipifarnib 200 mg/m2 per dose twice daily for 21 days repeated every 28 days. Patients who received enzyme-inducing anticonvulsants and other CYP3A4/5 inducers or inhibitors were excluded. The primary objective was to estimate the sustained response rate in all strata. RESULTS. Ninety-seven patients with a median age of 11.2 years (range, 3.2-21.9 years) were enrolled on the study, and 81 patients were evaluable for response. One of 35 patients with BSG and 1 of 31 patients with HGG had a sustained partial response. No responses were observed in 15 patients with MB/PNET. Eight patients (3 HGG, 1 MB, and 4 BSG) remained stable for ≥4 courses (range, 4-25 courses). The median number of courses received was 2 (range, 1-25 courses). The most frequent grade 3 and 4 toxicities included neutropenia (18.7%), thrombocytopenia (14.3%), and leukopenia (14.3%). The 6-month progression-free survival rate (±standard deviation) was 14% ± 6% for HGG, 6% ± 6% for MB/PNET and 3% ± 3% for BSG. CONCLUSIONS. Tipifarnib tolerated well but had little activity as a single agent in children with recurrent central nervous system malignancies.

AB - BACKGROUND. An open-label Phase II study of tipifarnib was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), high-grade glioma (HGG), and diffuse intrinsic brainstem glioma (BSG). METHODS. Between January 2004 and July 2005, patients were enrolled and stratified as follows: Stratum 1, recurrent or refractory MB/PNET; Stratum 2, recurrent or refractory HGG; and Stratum 3, recurrent or refractory BSG. Patients received tipifarnib 200 mg/m2 per dose twice daily for 21 days repeated every 28 days. Patients who received enzyme-inducing anticonvulsants and other CYP3A4/5 inducers or inhibitors were excluded. The primary objective was to estimate the sustained response rate in all strata. RESULTS. Ninety-seven patients with a median age of 11.2 years (range, 3.2-21.9 years) were enrolled on the study, and 81 patients were evaluable for response. One of 35 patients with BSG and 1 of 31 patients with HGG had a sustained partial response. No responses were observed in 15 patients with MB/PNET. Eight patients (3 HGG, 1 MB, and 4 BSG) remained stable for ≥4 courses (range, 4-25 courses). The median number of courses received was 2 (range, 1-25 courses). The most frequent grade 3 and 4 toxicities included neutropenia (18.7%), thrombocytopenia (14.3%), and leukopenia (14.3%). The 6-month progression-free survival rate (±standard deviation) was 14% ± 6% for HGG, 6% ± 6% for MB/PNET and 3% ± 3% for BSG. CONCLUSIONS. Tipifarnib tolerated well but had little activity as a single agent in children with recurrent central nervous system malignancies.

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