A phase i trial of temozolomide and lomustine in newly diagnosed high-grade gliomas of childhood

Regina I. Jakacki, Allan Yates, Susan M. Blaney, Tianni Zhou, Robert Timmerman, Ashish M. Ingle, Lynda Flom, Michael D. Prados, Peter C. Adamson, Ian F. Pollack

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23 Scopus citations


A phase I trial was conducted to determine the maximum tolerated dose (MTD) of temozolomide given in combination with lomustine in newly diagnosed pediatric patients with high-grade gliomas. Response was assessed following two courses of therapy at the MTD. Temozolomide was administered to cohorts of patients at doses of 100, 125, 160, or 200 mg/m 2 on days 1-5, along with 90 mg/m 2 lomustine on day 1. Two courses of lomustine/ temozolomide were given prior to radiation therapy (RT) and up to six courses were administered afterward. Thirty-two patients were enrolled. Dose-limiting myelosuppression was seen in two of three patients enrolled at the 200 mg/m 2 dose level. One of 14 patients in the expanded MTD cohort (160 mg/m 2) experienced dose-limiting thrombocytopenia. After two courses at the MTD, one patient with a 5-mm enhancing nodule postoperatively had a complete response, one patient with a large residual temporal lobe glioblastoma had a partial response, and eight patients had stable disease. Several patients developed transient radiographic worsening after completing RT. Median 1- and 2-year overall survivals at the MTD were 60% ± 13% and 40% ± 13% with a median of 17.6 months. Thirteen of 20 patients (65%) who underwent MRI scans within 6 months prior to death developed metastatic disease. In conclusion, when administered with 90 mg/m 2 lomustine on day 1, the MTD of temozolomide is 160 mg/m 2/day × 5. Radiographic changes following RT make determination of early tumor progression difficult. Metastatic disease is common prior to death.

Original languageEnglish (US)
Pages (from-to)569-576
Number of pages8
Issue number4
StatePublished - Aug 2008


  • CCNU (lomustine)
  • Malignant glioma
  • Pediatrics
  • Temozolomide

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research


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