Phase 2 study of concurrent radiotherapy and temozolomide followed by temozolomide and lomustine in the treatment of children with high-grade glioma: A report of the Children's Oncology Group ACNS0423 study

Regina I. Jakacki, Kenneth J. Cohen, Allen Buxton, Mark D. Krailo, Peter C. Burger, Marc K. Rosenblum, Daniel J. Brat, Ronald L. Hamilton, Sandrah P. Eckel, Tianni Zhou, Robert S. Lavey, Ian F. Pollack

Research output: Contribution to journalArticlepeer-review

Abstract

Background The prognosis for children with malignant glioma is poor. This study was designed to determine whether lomustine and temozolomide following radiotherapy and concurrent temozolomide improves event-free survival (EFS) compared with historical controls with anaplastic astrocytoma (AA) or glioblastoma (GBM) and whether survival is influenced by the expression of O6-methylguanine-DNA-methyltransferase (MGMT). Methods Following maximal surgical resection, newly diagnosed children with nonmetastatic high-grade glioma underwent involved field radiotherapy with concurrent temozolomide. Adjuvant chemotherapy consisted of up to 6 cycles of lomustine 90 mg/m2 on day 1 and temozolomide 160 mg/m2/day ×5 every 6 weeks. Results Among the 108 eligible patients with AA or GBM, 1-year EFS was 0.49 (95% CI, 0.39-0.58), similar to the original CCG-945-based design model. However, EFS and OS were significantly improved in ACNS0423 compared with the 86 AA or GBM participants treated with adjuvant temozolomide alone in the recent ACNS0126 study (1-sided log-rank P =. 019 and. 019, respectively). For example, 3-year EFS was 0.22 (95% CI, 0.14-0.30) in ACNS0423 compared with 0.11 (95% CI, 0.05-0.18) in ACNS0126. Stratifying the comparison by resection extent, the addition of lomustine resulted in significantly better EFS and OS in participants without gross-total resection (P =. 019 and. 00085 respectively). The difference in EFS and OS was most pronounced for participants with GBM (P =. 059 and 0.051, respectively), and those with MGMT overexpression (P =. 00036 and. 00038, respectively). Conclusion The addition of lomustine to temozolomide as adjuvant therapy in ACNS0423 was associated with significantly improved outcome compared with the preceding COG ACNS0126 HGG study in which participants received temozolomide alone.

Original languageEnglish (US)
Pages (from-to)1442-1450
Number of pages9
JournalNeuro-oncology
Volume18
Issue number10
DOIs
StatePublished - Oct 1 2016

Keywords

  • astrocytoma
  • glioblastoma
  • lomustine
  • pediatric high-grade glioma
  • temozolomide

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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