Phase II and pharmacogenomics study of enzastaurin plus temozolomide during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme and gliosarcoma

Nicholas Butowski, Susan M. Chang, Kathleen R. Lamborn, Mei-Yin Polley, Russell Pieper, Joseph F. Costello, Scott Vandenberg, Rupa Parvataneni, Angelina Nicole, Patricia K. Sneed, Jennifer Clarke, Emily Hsieh, Bruno M. Costa, Rui M. Reis, Maria Hristova-Kazmierski, Steven J. Nicol, Donald E. Thornton, Michael D. Prados

Research output: Contribution to journalArticle

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Abstract

This open-label, single-arm, phase II study combined enzastaurin with temozolomide plus radiation therapy (RT) to treat glioblastoma multiforme (GBM) and gliosarcoma. Adults with newly diagnosed disease and Karnofsky performance status (KPS) ≥ 60 were enrolled. Treatment was started within 5 weeks after surgical diagnosis. RT consisted of 60 Gy over 6 weeks. Temozolomide was given at 75 mg/m2 daily during RT and then adjuvantly at 200 mg/m2 daily for 5 days, followed by a 23-day break. Enzastaurin was given once daily during RT and in the adjuvant period at 250 mg/ day. Cycles were 28 days. The primary end point was overall survival (OS). Progression-free survival (PFS), toxicity, and correlations between efficacy and molecular markers analyzed from tumor tissue samples were also evaluated. A prospectively planned analysis compared OS and PFS of the current trial with outcomes from 3 historical phase II trials that combined novel agents with temozolomide plus RT in patients with GBM or gliosarcoma. Sixty-six patients were enrolled. The treatment regimen was well tolerated. OS (median, 74 weeks) and PFS (median, 36 weeks) results from the current trial were comparable to those from a prior phase II study using erlotininb and were significantly better than those from 2 other previous studies that used thalidomide or cis-retinoic acid, all in combination with temozolomide plus RT. A positive correlation between O-6-methylguanine- DNA methyltransferase promoter methylation and OS was observed. Adjusting for age and KPS, no other biomarker was associated with survival outcome. Correlation of relevant biomarkers with OS may be useful in future trials.

Original languageEnglish (US)
Pages (from-to)1331-1338
Number of pages8
JournalNeuro-Oncology
Volume13
Issue number12
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

Fingerprint

temozolomide
Gliosarcoma
Glioblastoma
Radiotherapy
Survival
Disease-Free Survival
Karnofsky Performance Status
NSC 153174
O(6)-Methylguanine-DNA Methyltransferase
Biomarkers
Thalidomide
Tumor Biomarkers
Tretinoin
Methylation
Pharmacogenomic Testing
enzastaurin

Keywords

  • Adjuvant therapy
  • Enzastaurin
  • Glioblastoma multiforme
  • Radiation therapy
  • Temozolomide.

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Phase II and pharmacogenomics study of enzastaurin plus temozolomide during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme and gliosarcoma. / Butowski, Nicholas; Chang, Susan M.; Lamborn, Kathleen R.; Polley, Mei-Yin; Pieper, Russell; Costello, Joseph F.; Vandenberg, Scott; Parvataneni, Rupa; Nicole, Angelina; Sneed, Patricia K.; Clarke, Jennifer; Hsieh, Emily; Costa, Bruno M.; Reis, Rui M.; Hristova-Kazmierski, Maria; Nicol, Steven J.; Thornton, Donald E.; Prados, Michael D.

In: Neuro-Oncology, Vol. 13, No. 12, 01.12.2011, p. 1331-1338.

Research output: Contribution to journalArticle

Butowski, N, Chang, SM, Lamborn, KR, Polley, M-Y, Pieper, R, Costello, JF, Vandenberg, S, Parvataneni, R, Nicole, A, Sneed, PK, Clarke, J, Hsieh, E, Costa, BM, Reis, RM, Hristova-Kazmierski, M, Nicol, SJ, Thornton, DE & Prados, MD 2011, 'Phase II and pharmacogenomics study of enzastaurin plus temozolomide during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme and gliosarcoma', Neuro-Oncology, vol. 13, no. 12, pp. 1331-1338. https://doi.org/10.1093/neuonc/nor130
Butowski, Nicholas ; Chang, Susan M. ; Lamborn, Kathleen R. ; Polley, Mei-Yin ; Pieper, Russell ; Costello, Joseph F. ; Vandenberg, Scott ; Parvataneni, Rupa ; Nicole, Angelina ; Sneed, Patricia K. ; Clarke, Jennifer ; Hsieh, Emily ; Costa, Bruno M. ; Reis, Rui M. ; Hristova-Kazmierski, Maria ; Nicol, Steven J. ; Thornton, Donald E. ; Prados, Michael D. / Phase II and pharmacogenomics study of enzastaurin plus temozolomide during and following radiation therapy in patients with newly diagnosed glioblastoma multiforme and gliosarcoma. In: Neuro-Oncology. 2011 ; Vol. 13, No. 12. pp. 1331-1338.
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AU - Pieper, Russell

AU - Costello, Joseph F.

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