Phase I/II trial of erlotinib and temozolomide with radiation therapy in the treatment of newly diagnosed glioblastoma multiforme: North Central Cancer Treatment Group Study N0177.
Publication/Presentation Date
12-1-2008
Abstract
PURPOSE: Epidermal growth factor receptor (EGFR) amplification in glioblastoma multiforme (GBM) is a common occurrence and is associated with treatment resistance. Erlotinib, a selective EGFR inhibitor, was combined with temozolomide (TMZ) and radiotherapy (RT) in a phase I/II trial.
PATIENTS AND METHODS: Adults not taking enzyme-inducing anticonvulsants after resection or biopsy of GBM were treated with erlotinib (150 mg daily) until progression. Erlotinib was delivered alone for 1 week, then concurrently with TMZ (75 mg mg/m(2) daily) and RT (60 Gy), and finally, concurrently with up to six cycles of adjuvant TMZ (200 mg/m(2) daily for 5 days every 28 days). The primary end point was survival at 1 year.
RESULTS: Ninety-seven eligible patients were accrued with a median follow-up time of 22.2 months. By definition, the primary end point was successfully met with a median survival time of 15.3 months. However, there was no sign of benefit in overall survival when comparing N0177 with the RT/TMZ arm of the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981/22981 (recursive partitioning analysis [RPA] class III, 19 v 21 months; RPA class IV, 16 v 16 months; RPA class V, 8 v 10 months, respectively). Presence of diarrhea, rash, and EGFRvIII, p53, phosphatase and tensin homolog (PTEN), combination EGFR and PTEN, and EGFR amplification status were not predictive (P > .05) of survival.
CONCLUSION: Although the primary end point was successfully met using nitrosourea-based (pre-TMZ) chemotherapy era historic controls, there was no sign of benefit compared with TMZ era controls. Analyses of molecular subsets did not reveal cohorts of patients sensitive to erlotinib. TMZ chemotherapy combined with RT resulted in improved outcomes compared with historical controls who received nitrosourea-based chemotherapies.
Volume
26
Issue
34
First Page
5603
Last Page
5609
ISSN
1527-7755
Published In/Presented At
Brown, P. D., Krishnan, S., Sarkaria, J. N., Wu, W., Jaeckle, K. A., Uhm, J. H., Geoffroy, F. J., Arusell, R., Kitange, G., Jenkins, R. B., Kugler, J. W., Morton, R. F., Rowland, K. M., Jr, Mischel, P., Yong, W. H., Scheithauer, B. W., Schiff, D., Giannini, C., Buckner, J. C., & North Central Cancer Treatment Group Study N0177 (2008). Phase I/II trial of erlotinib and temozolomide with radiation therapy in the treatment of newly diagnosed glioblastoma multiforme: North Central Cancer Treatment Group Study N0177. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 26(34), 5603–5609. https://doi.org/10.1200/JCO.2008.18.0612
Disciplines
Medicine and Health Sciences
PubMedID
18955445
Department(s)
Hematology-Medical Oncology Division, Lehigh Valley Topper Cancer Institute
Document Type
Article