Phase 2 trial of pemetrexed in children and adolescents with refractory solid tumors: A Children's Oncology Group study

Anne B. Warwick, Suman Malempati, Mark Krailo, Allen Melemed, Richard Gorlick, Matthew M. Ames, Stephanie L. Safgren, Peter C. Adamson, Susan M. Blaney

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Pemetrexed is a multi-targeted antifolate that inhibits key enzymes involved in nucleotide biosynthesis. We performed a phase 2 trial of pemetrexed in children with refractory or recurrent solid tumors, including CNS tumors, to estimate the response rate and further define its toxicity profile. Procedure: Pemetrexed, at a dose of 1910mg/m2, was administered as a 10-minute intravenous infusion every 21 days. Patients also received vitamin B12, daily multivitamin supplementation, and dexamethasone. A two-stage design (10+10) was employed in each of the following disease strata: osteosarcoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET, and non-brainstem high-grade glioma. Results: Seventy-two eligible subjects (39 males) were enrolled. Median age was 11 years (range 3-23). Sixty-eight were evaluable for response. The median number of cycles administered was 2 (range 1-13). No complete or partial responses were observed. Stable disease, for a median of 5 (range 4-13) cycles, was observed in five patients (ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma; n=1 each). Neutropenia (44%), anemia (35%), and elevated alanine transaminase (35%) attributable to pemetrexed were the most commonly recurring toxicities observed in patients receiving multiple cycles. Other toxicities attributed to pemetrexed occurring in ≥10% of cycles included thrombocytopenia (30%), fatigue (18%), nausea (14), hyperglycemia (13%), rash (11%), vomiting (13%), and hypophosphatemia (11%). Conclusions: Pemetrexed, administered as an intravenous infusion every 21 days, was tolerable in children and adolescents with refractory solid tumors, including CNS tumors, but did not show evidence of objective anti-tumor activity in the childhood tumors studied.

Original languageEnglish (US)
Pages (from-to)237-241
Number of pages5
JournalPediatric Blood and Cancer
Volume60
Issue number2
DOIs
StatePublished - Feb 2013

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Pemetrexed
Ependymoma
Neoplasms
Medulloblastoma
Ewing's Sarcoma
Osteosarcoma
Neuroblastoma
Intravenous Infusions
Peripheral Primitive Neuroectodermal Tumors
Hypophosphatemia
Folic Acid Antagonists
Primitive Neuroectodermal Tumors
Rhabdomyosarcoma
Vitamin B 12
Exanthema
Neutropenia
Alanine Transaminase
Glioma
Hyperglycemia
Thrombocytopenia

Keywords

  • Antifolate
  • Pemetrexed
  • Phase 2

ASJC Scopus subject areas

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

Cite this

Phase 2 trial of pemetrexed in children and adolescents with refractory solid tumors : A Children's Oncology Group study. / Warwick, Anne B.; Malempati, Suman; Krailo, Mark; Melemed, Allen; Gorlick, Richard; Ames, Matthew M.; Safgren, Stephanie L.; Adamson, Peter C.; Blaney, Susan M.

In: Pediatric Blood and Cancer, Vol. 60, No. 2, 02.2013, p. 237-241.

Research output: Contribution to journalArticle

Warwick, AB, Malempati, S, Krailo, M, Melemed, A, Gorlick, R, Ames, MM, Safgren, SL, Adamson, PC & Blaney, SM 2013, 'Phase 2 trial of pemetrexed in children and adolescents with refractory solid tumors: A Children's Oncology Group study', Pediatric Blood and Cancer, vol. 60, no. 2, pp. 237-241. https://doi.org/10.1002/pbc.24244
Warwick, Anne B. ; Malempati, Suman ; Krailo, Mark ; Melemed, Allen ; Gorlick, Richard ; Ames, Matthew M. ; Safgren, Stephanie L. ; Adamson, Peter C. ; Blaney, Susan M. / Phase 2 trial of pemetrexed in children and adolescents with refractory solid tumors : A Children's Oncology Group study. In: Pediatric Blood and Cancer. 2013 ; Vol. 60, No. 2. pp. 237-241.
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abstract = "Background: Pemetrexed is a multi-targeted antifolate that inhibits key enzymes involved in nucleotide biosynthesis. We performed a phase 2 trial of pemetrexed in children with refractory or recurrent solid tumors, including CNS tumors, to estimate the response rate and further define its toxicity profile. Procedure: Pemetrexed, at a dose of 1910mg/m2, was administered as a 10-minute intravenous infusion every 21 days. Patients also received vitamin B12, daily multivitamin supplementation, and dexamethasone. A two-stage design (10+10) was employed in each of the following disease strata: osteosarcoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET, and non-brainstem high-grade glioma. Results: Seventy-two eligible subjects (39 males) were enrolled. Median age was 11 years (range 3-23). Sixty-eight were evaluable for response. The median number of cycles administered was 2 (range 1-13). No complete or partial responses were observed. Stable disease, for a median of 5 (range 4-13) cycles, was observed in five patients (ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma; n=1 each). Neutropenia (44{\%}), anemia (35{\%}), and elevated alanine transaminase (35{\%}) attributable to pemetrexed were the most commonly recurring toxicities observed in patients receiving multiple cycles. Other toxicities attributed to pemetrexed occurring in ≥10{\%} of cycles included thrombocytopenia (30{\%}), fatigue (18{\%}), nausea (14), hyperglycemia (13{\%}), rash (11{\%}), vomiting (13{\%}), and hypophosphatemia (11{\%}). Conclusions: Pemetrexed, administered as an intravenous infusion every 21 days, was tolerable in children and adolescents with refractory solid tumors, including CNS tumors, but did not show evidence of objective anti-tumor activity in the childhood tumors studied.",
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AU - Krailo, Mark

AU - Melemed, Allen

AU - Gorlick, Richard

AU - Ames, Matthew M.

AU - Safgren, Stephanie L.

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N2 - Background: Pemetrexed is a multi-targeted antifolate that inhibits key enzymes involved in nucleotide biosynthesis. We performed a phase 2 trial of pemetrexed in children with refractory or recurrent solid tumors, including CNS tumors, to estimate the response rate and further define its toxicity profile. Procedure: Pemetrexed, at a dose of 1910mg/m2, was administered as a 10-minute intravenous infusion every 21 days. Patients also received vitamin B12, daily multivitamin supplementation, and dexamethasone. A two-stage design (10+10) was employed in each of the following disease strata: osteosarcoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET, and non-brainstem high-grade glioma. Results: Seventy-two eligible subjects (39 males) were enrolled. Median age was 11 years (range 3-23). Sixty-eight were evaluable for response. The median number of cycles administered was 2 (range 1-13). No complete or partial responses were observed. Stable disease, for a median of 5 (range 4-13) cycles, was observed in five patients (ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma; n=1 each). Neutropenia (44%), anemia (35%), and elevated alanine transaminase (35%) attributable to pemetrexed were the most commonly recurring toxicities observed in patients receiving multiple cycles. Other toxicities attributed to pemetrexed occurring in ≥10% of cycles included thrombocytopenia (30%), fatigue (18%), nausea (14), hyperglycemia (13%), rash (11%), vomiting (13%), and hypophosphatemia (11%). Conclusions: Pemetrexed, administered as an intravenous infusion every 21 days, was tolerable in children and adolescents with refractory solid tumors, including CNS tumors, but did not show evidence of objective anti-tumor activity in the childhood tumors studied.

AB - Background: Pemetrexed is a multi-targeted antifolate that inhibits key enzymes involved in nucleotide biosynthesis. We performed a phase 2 trial of pemetrexed in children with refractory or recurrent solid tumors, including CNS tumors, to estimate the response rate and further define its toxicity profile. Procedure: Pemetrexed, at a dose of 1910mg/m2, was administered as a 10-minute intravenous infusion every 21 days. Patients also received vitamin B12, daily multivitamin supplementation, and dexamethasone. A two-stage design (10+10) was employed in each of the following disease strata: osteosarcoma, Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET), rhabdomyosarcoma, neuroblastoma, ependymoma, medulloblastoma/supratentorial PNET, and non-brainstem high-grade glioma. Results: Seventy-two eligible subjects (39 males) were enrolled. Median age was 11 years (range 3-23). Sixty-eight were evaluable for response. The median number of cycles administered was 2 (range 1-13). No complete or partial responses were observed. Stable disease, for a median of 5 (range 4-13) cycles, was observed in five patients (ependymoma, Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma; n=1 each). Neutropenia (44%), anemia (35%), and elevated alanine transaminase (35%) attributable to pemetrexed were the most commonly recurring toxicities observed in patients receiving multiple cycles. Other toxicities attributed to pemetrexed occurring in ≥10% of cycles included thrombocytopenia (30%), fatigue (18%), nausea (14), hyperglycemia (13%), rash (11%), vomiting (13%), and hypophosphatemia (11%). Conclusions: Pemetrexed, administered as an intravenous infusion every 21 days, was tolerable in children and adolescents with refractory solid tumors, including CNS tumors, but did not show evidence of objective anti-tumor activity in the childhood tumors studied.

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