Abstract | PURPOSE: PATIENTS AND METHODS: Sixty-five eligible adults with newly diagnosed GBM or gliosarcoma were enrolled. We intended to treat patients not currently treated with enzyme-inducing antiepileptic drugs (EIAEDs) with 100 mg/d of erlotinib during XRT and 150 mg/d after XRT. Patients receiving EIAEDs were to receive 200 mg/d of erlotinib during XRT and 300 mg/d after XRT. After XRT, the erlotinib dose was escalated until patients developed tolerable grade 2 rash or until the maximum allowed dose was reached. All patients received temozolomide during and after XRT. Molecular markers of epidermal growth factor receptor (EGFR), EGFRvIII, phosphatase and tensin homolog (PTEN), and methylation status of the promotor region of the MGMT gene were analyzed from tumor tissue. Survival was compared with outcomes from two historical phase II trials. RESULTS: Median survival was 19.3 months in the current study and 14.1 months in the combined historical control studies, with a hazard ratio for survival (treated/control) of 0.64 (95% CI, 0.45 to 0.91). Treatment was well tolerated. There was a strong positive correlation between MGMT promotor methylation and survival, as well as an association between MGMT promotor-methylated tumors and PTEN positivity shown by immunohistochemistry with improved survival. CONCLUSION: Patients treated with the combination of erlotinib and temozolomide during and following radiotherapy had better survival than historical controls. Additional studies are warranted.
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Authors | Michael D Prados, Susan M Chang, Nicholas Butowski, Rebecca DeBoer, Rupa Parvataneni, Hannah Carliner, Paul Kabuubi, Jennifer Ayers-Ringler, Jane Rabbitt, Margaretta Page, Anne Fedoroff, Penny K Sneed, Mitchel S Berger, Michael W McDermott, Andrew T Parsa, Scott Vandenberg, C David James, Kathleen R Lamborn, David Stokoe, Daphne A Haas-Kogan |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 27
Issue 4
Pg. 579-84
(Feb 01 2009)
ISSN: 1527-7755 [Electronic] United States |
PMID | 19075262
(Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Alkylating
- Protein Kinase Inhibitors
- Quinazolines
- Dacarbazine
- Erlotinib Hydrochloride
- Temozolomide
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Topics |
- Adult
- Aged
- Antineoplastic Agents, Alkylating
(administration & dosage)
- Brain Neoplasms
(drug therapy, mortality, radiotherapy)
- Combined Modality Therapy
- Dacarbazine
(administration & dosage, analogs & derivatives)
- Erlotinib Hydrochloride
- Glioblastoma
(drug therapy, mortality, radiotherapy)
- Gliosarcoma
(drug therapy, mortality, radiotherapy)
- Humans
- Middle Aged
- Protein Kinase Inhibitors
(administration & dosage)
- Quinazolines
(administration & dosage)
- Temozolomide
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