PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation: A Randomized Phase II Study: BrUOG 244

Heinrich Elinzano, Michael Glantz, Maciej Mrugala, Santosh Kesari, David E. Piccioni, Lyndon Kim, Edward Pan, Shakeeb Yunus, Thomas Coyle, Kinsella Timothy, Devon Evans, Kalyan Mantripragada, Jerrold Boxerman, Thomas DiPetrillo, John E. Donahue, Nicholas Hebda, Kristen M. Mitchell, Kayla L. Rosati, Howard Safran

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Abstract

PURPOSE:: Efficacy signals but substantial myelosuppression were demonstrated in a single arm phase II study of paclitaxel poliglumex (PPX) in combination with temozolomide (TMZ) and radiation therapy (RT) for first-line treatment of glioblastoma. The objective of this randomized phase II trial was to assess the efficacy and safety of single-agent PPX with RT (PPX/RT) versus TMZ with RT (TMZ/RT) for glioblastoma without O-methylguanine-DNA methyltransferase (MGMT) methylation. MATERIALS AND METHODS:: Patients with glioblastoma with unmethylated MGMT without prior chemotherapy or RT were eligible. Patients were randomly assigned 2:1 to PPX, 50 mg/m/wk for 6 weeks, or standard TMZ, with concurrent 60.0 Gy RT. One month after completion of chemoradiation all patients received standard maintenance TMZ. The primary endpoint was progression-free survival (PFS). RESULTS:: Of the 164 patients enrolled, 86 were MGMT unmethylated. Of these, 63 patients were randomized (42 to PPX/RT and 21 to TMZ/RT). Fifty-nine patients could be analyzed. The median PFS was 9 months in the PPX/RT group and 9.5 months in the TMZ/RT group (hazard ratio in the PPX/RT group, 1.10; 95% confidence interval, 0.79-2.08; P=0.75). Median overall survival was 16 versus 14.8 months for PPX/RT and TMZ/RT groups, respectively (hazard ratio, 1.44; 95% confidence interval, 0.75-2.77; P=0.27). In the PPX and TMZ groups 44% versus 22% of patients, respectively, experienced one or more grade 3 or higher toxicities during chemoradiation. CONCLUSIONS:: PPX/RT did not improve PFS or overall survival. This study provides an effective trial design for screening RT sensitizers in glioblastoma.

Original languageEnglish (US)
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
DOIs
StateAccepted/In press - Dec 9 2015

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Elinzano, H., Glantz, M., Mrugala, M., Kesari, S., Piccioni, D. E., Kim, L., Pan, E., Yunus, S., Coyle, T., Timothy, K., Evans, D., Mantripragada, K., Boxerman, J., DiPetrillo, T., Donahue, J. E., Hebda, N., Mitchell, K. M., Rosati, K. L., & Safran, H. (Accepted/In press). PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation: A Randomized Phase II Study: BrUOG 244. American Journal of Clinical Oncology: Cancer Clinical Trials. https://doi.org/10.1097/COC.0000000000000247