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

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24 Scopus citations

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 1 2013

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Keywords

  • Antifolate
  • Pemetrexed
  • Phase 2

ASJC Scopus subject areas

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

Cite this

Warwick, A. B., Malempati, S., Krailo, M., Melemed, A., Gorlick, R., Ames, M. M., Safgren, S. L., Adamson, P. C., & Blaney, S. M. (2013). Phase 2 trial of pemetrexed in children and adolescents with refractory solid tumors: A Children's Oncology Group study. Pediatric Blood and Cancer, 60(2), 237-241. https://doi.org/10.1002/pbc.24244