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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 O6-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/m2/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)
Pages (from-to)159-162
Number of pages4
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume41
Issue number2
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Fingerprint

temozolomide
Methyltransferases
DNA Methylation
Glioblastoma
Radiotherapy
Radiation
Disease-Free Survival
paclitaxel poliglumex
Confidence Intervals
Radiation-Sensitizing Agents
Radiation Dosage
Survival
DNA

Keywords

  • GBM
  • methylation
  • MGMT
  • paclitaxel polyglumex
  • radiation
  • radiation
  • temozolomide
  • unmethylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation : A Randomized Phase II Study: BrUOG 244. / Elinzano, Heinrich; Glantz, Michael; Mrugala, Maciej; Kesari, Santosh; Piccioni, David E.; Kim, Lyndon; Pan, Edward; Yunus, Shakeeb; Coyle, Thomas; Timothy, Kinsella; Evans, Devon; Mantripragada, Kalyan; Boxerman, Jerrold; DiPetrillo, Thomas; Donahue, John E.; Hebda, Nicholas; Mitchell, Kristen M.; Rosati, Kayla L.; Safran, Howard.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 41, No. 2, 01.01.2018, p. 159-162.

Research output: Contribution to journalArticle

Elinzano, H, Glantz, M, Mrugala, M, Kesari, S, Piccioni, DE, Kim, L, Pan, E, Yunus, S, Coyle, T, Timothy, K, Evans, D, Mantripragada, K, Boxerman, J, DiPetrillo, T, Donahue, JE, Hebda, N, Mitchell, KM, Rosati, KL & Safran, H 2018, '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, vol. 41, no. 2, pp. 159-162. https://doi.org/10.1097/COC.0000000000000247
Elinzano, Heinrich ; Glantz, Michael ; Mrugala, Maciej ; Kesari, Santosh ; Piccioni, David E. ; Kim, Lyndon ; Pan, Edward ; Yunus, Shakeeb ; Coyle, Thomas ; Timothy, Kinsella ; Evans, Devon ; Mantripragada, Kalyan ; Boxerman, Jerrold ; DiPetrillo, Thomas ; Donahue, John E. ; Hebda, Nicholas ; Mitchell, Kristen M. ; Rosati, Kayla L. ; Safran, Howard. / PPX and Concurrent Radiation for Newly Diagnosed Glioblastoma Without MGMT Methylation : A Randomized Phase II Study: BrUOG 244. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 2018 ; Vol. 41, No. 2. pp. 159-162.
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T2 - A Randomized Phase II Study: BrUOG 244

AU - Elinzano, Heinrich

AU - Glantz, Michael

AU - Mrugala, Maciej

AU - Kesari, Santosh

AU - Piccioni, David E.

AU - Kim, Lyndon

AU - Pan, Edward

AU - Yunus, Shakeeb

AU - Coyle, Thomas

AU - Timothy, Kinsella

AU - Evans, Devon

AU - Mantripragada, Kalyan

AU - Boxerman, Jerrold

AU - DiPetrillo, Thomas

AU - Donahue, John E.

AU - Hebda, Nicholas

AU - Mitchell, Kristen M.

AU - Rosati, Kayla L.

AU - Safran, Howard

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N2 - 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 O6-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/m2/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.

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KW - GBM

KW - methylation

KW - MGMT

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KW - radiation

KW - radiation

KW - temozolomide

KW - unmethylation

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