A pediatric brain tumor consortium phase II trial of capecitabine rapidly disintegrating tablets with concomitant radiation therapy in children with newly diagnosed diffuse intrinsic pontine gliomas

Lindsay B. Kilburn, Mehmet Kocak, Patricia Baxter, Tina Young Poussaint, Arnold C. Paulino, Christine McIntyre, Annabelle Lemenuel-Diot, Christine Lopez-Diaz, Larry Kun, Murali Chintagumpala, Jack M. Su, Alberto Broniscer, Justin N. Baker, Eugene I. Hwang, Maryam Fouladi, James M. Boyett, Susan M. Blaney

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG). Patients and methods: Children 3–17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m 2 /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks starting the first day of RT. Following a 2-week break, three courses of capecitabine, 1,250 mg/m 2 /dose BID for 14 days followed by a 7-day rest, were administered. As prospectively designed, 10 evaluable patients treated at the MTD on the phase I trial were included in the phase II analyses. The design was based on comparison of the PFS distribution to a contemporary historical control (n = 140) with 90% power to detect a 15% absolute improvement in the 1-year PFS with a type-1 error rate, α = 0.10. Results: Forty-four patients were evaluable for the phase II objectives. Capecitabine and RT was well tolerated with low-grade palmar plantar erythrodyesthesia, increased alanine aminotransferase, cytopenias, and vomiting the most commonly reported toxicities. Findings were significant for earlier progression with 1-year PFS of 7.21% (SE = 3.47%) in the capecitabine-treated cohort versus 15.59% (SE = 3.05%) in the historical control (P = 0.007), but there was no difference for overall survival (OS) distributions (P = 0.30). Tumor enhancement at diagnosis was associated with shorter PFS and OS. Capecitabine was rapidly absorbed and converted to its metabolites. Conclusion: Capecitabine did not improve the outcome for children with newly diagnosed DIPG.

Original languageEnglish (US)
Article numbere26832
JournalPediatric Blood and Cancer
Volume65
Issue number2
DOIs
StatePublished - Feb 1 2018

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Brain Neoplasms
Glioma
Tablets
Radiotherapy
Pediatrics
Disease-Free Survival
Maximum Tolerated Dose
Survival
Capecitabine
Alanine Transaminase
Vomiting
Radiation
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

A pediatric brain tumor consortium phase II trial of capecitabine rapidly disintegrating tablets with concomitant radiation therapy in children with newly diagnosed diffuse intrinsic pontine gliomas. / Kilburn, Lindsay B.; Kocak, Mehmet; Baxter, Patricia; Poussaint, Tina Young; Paulino, Arnold C.; McIntyre, Christine; Lemenuel-Diot, Annabelle; Lopez-Diaz, Christine; Kun, Larry; Chintagumpala, Murali; Su, Jack M.; Broniscer, Alberto; Baker, Justin N.; Hwang, Eugene I.; Fouladi, Maryam; Boyett, James M.; Blaney, Susan M.

In: Pediatric Blood and Cancer, Vol. 65, No. 2, e26832, 01.02.2018.

Research output: Contribution to journalArticle

Kilburn, LB, Kocak, M, Baxter, P, Poussaint, TY, Paulino, AC, McIntyre, C, Lemenuel-Diot, A, Lopez-Diaz, C, Kun, L, Chintagumpala, M, Su, JM, Broniscer, A, Baker, JN, Hwang, EI, Fouladi, M, Boyett, JM & Blaney, SM 2018, 'A pediatric brain tumor consortium phase II trial of capecitabine rapidly disintegrating tablets with concomitant radiation therapy in children with newly diagnosed diffuse intrinsic pontine gliomas', Pediatric Blood and Cancer, vol. 65, no. 2, e26832. https://doi.org/10.1002/pbc.26832
Kilburn, Lindsay B. ; Kocak, Mehmet ; Baxter, Patricia ; Poussaint, Tina Young ; Paulino, Arnold C. ; McIntyre, Christine ; Lemenuel-Diot, Annabelle ; Lopez-Diaz, Christine ; Kun, Larry ; Chintagumpala, Murali ; Su, Jack M. ; Broniscer, Alberto ; Baker, Justin N. ; Hwang, Eugene I. ; Fouladi, Maryam ; Boyett, James M. ; Blaney, Susan M. / A pediatric brain tumor consortium phase II trial of capecitabine rapidly disintegrating tablets with concomitant radiation therapy in children with newly diagnosed diffuse intrinsic pontine gliomas. In: Pediatric Blood and Cancer. 2018 ; Vol. 65, No. 2.
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abstract = "Background: We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG). Patients and methods: Children 3–17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m 2 /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks starting the first day of RT. Following a 2-week break, three courses of capecitabine, 1,250 mg/m 2 /dose BID for 14 days followed by a 7-day rest, were administered. As prospectively designed, 10 evaluable patients treated at the MTD on the phase I trial were included in the phase II analyses. The design was based on comparison of the PFS distribution to a contemporary historical control (n = 140) with 90{\%} power to detect a 15{\%} absolute improvement in the 1-year PFS with a type-1 error rate, α = 0.10. Results: Forty-four patients were evaluable for the phase II objectives. Capecitabine and RT was well tolerated with low-grade palmar plantar erythrodyesthesia, increased alanine aminotransferase, cytopenias, and vomiting the most commonly reported toxicities. Findings were significant for earlier progression with 1-year PFS of 7.21{\%} (SE = 3.47{\%}) in the capecitabine-treated cohort versus 15.59{\%} (SE = 3.05{\%}) in the historical control (P = 0.007), but there was no difference for overall survival (OS) distributions (P = 0.30). Tumor enhancement at diagnosis was associated with shorter PFS and OS. Capecitabine was rapidly absorbed and converted to its metabolites. Conclusion: Capecitabine did not improve the outcome for children with newly diagnosed DIPG.",
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T1 - A pediatric brain tumor consortium phase II trial of capecitabine rapidly disintegrating tablets with concomitant radiation therapy in children with newly diagnosed diffuse intrinsic pontine gliomas

AU - Kilburn, Lindsay B.

AU - Kocak, Mehmet

AU - Baxter, Patricia

AU - Poussaint, Tina Young

AU - Paulino, Arnold C.

AU - McIntyre, Christine

AU - Lemenuel-Diot, Annabelle

AU - Lopez-Diaz, Christine

AU - Kun, Larry

AU - Chintagumpala, Murali

AU - Su, Jack M.

AU - Broniscer, Alberto

AU - Baker, Justin N.

AU - Hwang, Eugene I.

AU - Fouladi, Maryam

AU - Boyett, James M.

AU - Blaney, Susan M.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Background: We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG). Patients and methods: Children 3–17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m 2 /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks starting the first day of RT. Following a 2-week break, three courses of capecitabine, 1,250 mg/m 2 /dose BID for 14 days followed by a 7-day rest, were administered. As prospectively designed, 10 evaluable patients treated at the MTD on the phase I trial were included in the phase II analyses. The design was based on comparison of the PFS distribution to a contemporary historical control (n = 140) with 90% power to detect a 15% absolute improvement in the 1-year PFS with a type-1 error rate, α = 0.10. Results: Forty-four patients were evaluable for the phase II objectives. Capecitabine and RT was well tolerated with low-grade palmar plantar erythrodyesthesia, increased alanine aminotransferase, cytopenias, and vomiting the most commonly reported toxicities. Findings were significant for earlier progression with 1-year PFS of 7.21% (SE = 3.47%) in the capecitabine-treated cohort versus 15.59% (SE = 3.05%) in the historical control (P = 0.007), but there was no difference for overall survival (OS) distributions (P = 0.30). Tumor enhancement at diagnosis was associated with shorter PFS and OS. Capecitabine was rapidly absorbed and converted to its metabolites. Conclusion: Capecitabine did not improve the outcome for children with newly diagnosed DIPG.

AB - Background: We conducted a phase II study of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy (RT) to assess progression-free survival (PFS) in children with newly diagnosed diffuse intrinsic pontine gliomas (DIPG). Patients and methods: Children 3–17 years with newly diagnosed DIPG were eligible. Capecitabine, 650 mg/m 2 /dose BID (maximum tolerated dose [MTD] in children with concurrent radiation), was administered for 9 weeks starting the first day of RT. Following a 2-week break, three courses of capecitabine, 1,250 mg/m 2 /dose BID for 14 days followed by a 7-day rest, were administered. As prospectively designed, 10 evaluable patients treated at the MTD on the phase I trial were included in the phase II analyses. The design was based on comparison of the PFS distribution to a contemporary historical control (n = 140) with 90% power to detect a 15% absolute improvement in the 1-year PFS with a type-1 error rate, α = 0.10. Results: Forty-four patients were evaluable for the phase II objectives. Capecitabine and RT was well tolerated with low-grade palmar plantar erythrodyesthesia, increased alanine aminotransferase, cytopenias, and vomiting the most commonly reported toxicities. Findings were significant for earlier progression with 1-year PFS of 7.21% (SE = 3.47%) in the capecitabine-treated cohort versus 15.59% (SE = 3.05%) in the historical control (P = 0.007), but there was no difference for overall survival (OS) distributions (P = 0.30). Tumor enhancement at diagnosis was associated with shorter PFS and OS. Capecitabine was rapidly absorbed and converted to its metabolites. Conclusion: Capecitabine did not improve the outcome for children with newly diagnosed DIPG.

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