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

Research output: Contribution to journalArticle

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Abstract

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
JournalNeuro-Oncology
Volume10
Issue number4
DOIs
StatePublished - Aug 2008

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temozolomide
Lomustine
Glioma
Maximum Tolerated Dose
Radiotherapy

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Jakacki, R. I., Yates, A., Blaney, S. M., Zhou, T., Timmerman, R., Ingle, A. M., ... Pollack, I. F. (2008). A phase i trial of temozolomide and lomustine in newly diagnosed high-grade gliomas of childhood. Neuro-Oncology, 10(4), 569-576. https://doi.org/10.1215/15228517-2008-019

A phase i trial of temozolomide and lomustine in newly diagnosed high-grade gliomas of childhood. / Jakacki, Regina I.; Yates, Allan; Blaney, Susan M.; Zhou, Tianni; Timmerman, Robert; Ingle, Ashish M.; Flom, Lynda; Prados, Michael D.; Adamson, Peter C.; Pollack, Ian F.

In: Neuro-Oncology, Vol. 10, No. 4, 08.2008, p. 569-576.

Research output: Contribution to journalArticle

Jakacki, RI, Yates, A, Blaney, SM, Zhou, T, Timmerman, R, Ingle, AM, Flom, L, Prados, MD, Adamson, PC & Pollack, IF 2008, 'A phase i trial of temozolomide and lomustine in newly diagnosed high-grade gliomas of childhood', Neuro-Oncology, vol. 10, no. 4, pp. 569-576. https://doi.org/10.1215/15228517-2008-019
Jakacki, Regina I. ; Yates, Allan ; Blaney, Susan M. ; Zhou, Tianni ; Timmerman, Robert ; Ingle, Ashish M. ; Flom, Lynda ; Prados, Michael D. ; Adamson, Peter C. ; Pollack, Ian F. / A phase i trial of temozolomide and lomustine in newly diagnosed high-grade gliomas of childhood. In: Neuro-Oncology. 2008 ; Vol. 10, No. 4. pp. 569-576.
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abstract = "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.",
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