Clinical Trial

. 2018 Apr 1;100(5):1195-1203.

doi: 10.1016/j.ijrobp.2018.01.001. Epub 2018 Jan 6.

Phase 2 Study of Bortezomib Combined With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Safety and Efficacy Assessment

Affiliations

¹ Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California; Department of Neurology, School of Medicine at University of California, Irvine, Irvine, California.
² Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
³ School of Public Health, Xinxiang Medical University, Xinxiang, China, and Curtin University, Perth, Western Australia, Australia.
⁴ Department of Pathology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
⁵ Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
⁶ Kaiser Permanente Southern California, Los Angeles, California.
⁷ Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
⁸ Department of Radiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
⁹ Department of Neurology, Columbia University, New York, New York.
¹⁰ Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. Electronic address: albertlai@mednet.ucla.edu.

PMID: 29722661
PMCID: PMC6277207
DOI: 10.1016/j.ijrobp.2018.01.001

Clinical Trial

Phase 2 Study of Bortezomib Combined With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Safety and Efficacy Assessment

Xiao-Tang Kong et al. Int J Radiat Oncol Biol Phys. 2018.

. 2018 Apr 1;100(5):1195-1203.

doi: 10.1016/j.ijrobp.2018.01.001. Epub 2018 Jan 6.

Authors

Affiliations

¹ Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California; Department of Neurology, School of Medicine at University of California, Irvine, Irvine, California.
² Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
³ School of Public Health, Xinxiang Medical University, Xinxiang, China, and Curtin University, Perth, Western Australia, Australia.
⁴ Department of Pathology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
⁵ Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
⁶ Kaiser Permanente Southern California, Los Angeles, California.
⁷ Department of Radiation Oncology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
⁸ Department of Radiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
⁹ Department of Neurology, Columbia University, New York, New York.
¹⁰ Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California. Electronic address: albertlai@mednet.ucla.edu.

PMID: 29722661
PMCID: PMC6277207
DOI: 10.1016/j.ijrobp.2018.01.001

Erratum in

Erratum to: Kong X-T, Nguyen NT, Choi YJ, et al. Phase 2 Study of Bortezomib Combined With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Safety and Efficacy Assessment. Int J Radiat Oncol Biol Phys 2018;100:1195-1203.
[No authors listed] [No authors listed] Int J Radiat Oncol Biol Phys. 2019 Apr 1;103(5):1289. doi: 10.1016/j.ijrobp.2019.01.071. Epub 2019 Mar 13. Int J Radiat Oncol Biol Phys. 2019. PMID: 30900570 No abstract available.

Abstract

Purpose: To assess the safety and efficacy of upfront treatment using bortezomib combined with standard radiation therapy (RT) and temozolomide (TMZ), followed by adjuvant bortezomib and TMZ for ≤24 cycles, in patients with newly diagnosed glioblastoma multiforme (GBM).

Methods and materials: Twenty-four patients with newly diagnosed GBM were enrolled. The patients received standard external beam regional RT with concurrent TMZ beginning 3 to 6 weeks after surgery, followed by adjuvant TMZ and bortezomib for ≤24 cycles or until tumor progression. During RT, bortezomib was given at 1.3 mg/m² on days 1, 4, 8, 11, 29, 32, 36, and 39. After RT, bortezomib was given at 1.3 mg/m² on days 1, 4, 8, and 11 every 4 weeks.

Results: No unexpected adverse events occurred from the addition of bortezomib. The efficacy analysis showed a median progression-free survival (PFS) of 6.2 months (95% confidence interval [CI] 3.7-8.8), with promising PFS rates at ≥18 months compared with historical norms (25.0% at 18 and 24 months; 16.7% at 30 months). In terms of overall survival (OS), the median OS was 19.1 months (95% CI 6.7-31.4), with improved OS rates at ≥12 months (87.5% at 12, 50.0% at 24, 34.1% at 36-60 months) compared with the historical norms. The median PFS was 24.7 months (95% CI 8.5-41.0) in 10 MGMT methylated and 5.1 months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61 months (95% CI upper bound not reached) in the methylated and 16.4 months (95% CI 11.8-21.0) in the unmethylated patients.

Conclusions: The addition of bortezomib to current standard radiochemotherapy in newly diagnosed GBM patients was tolerable. The PFS and OS rates appeared promising, with more benefit to MGMT methylated patients. Further clinical investigation is warranted in a larger cohort of patients.

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Conflict of interest statement

Conflict of interest:

The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Xiao-Tang Kong MD PhD

Nhung T. Nguyen

Yoon J. Choi MD

Guicheng Zhang, MD PhD

HuyTram N. Nguyen

Emese Filka MD

Stacey Green MSN

P. Leia Nghiemphu MD

William H. Yong MD

Linda M. Liau MD PhD

Tania Kaprealian MD

Whitney B. Pope MD PhD

Andrew Lassman, MD

Tim Cloughesy MD

The authors whose names are listed immediately below report the following details of affiliation or involvement in an organization or entity with a financial or non-financial interest in the subject matter or materials discussed in this manuscript. Please specify the nature of the conflict on a separate sheet of paper if the space below is inadequate.

Albert Lai, MD, PhD – Grant from Millennium/Takeda (This is an investigator initiated industry sponsored study)

**Author disclosure forms from all authors were uploaded.

Figures

**Figure 1.. Treatment and Evaluation Plan**
**Study Regimen**: Bortezomib is given intravenously/subcutaneously at 1.3 mg/ m² on days 1, 4, 8, 11, 29, 32, 36, and 39 during radiation as early as 14 days after surgery. Temozolomide is given daily (75mg/m²) during radiation, followed by 5 days out of 28 with a dosage of 150–200 mg/m², for up to 24 cycles. Bortezomib at 1.3 mg/m² is given on days 1, 4, 8, and 11 of each subsequent 28 day cycle. Both bortezomib and temozolomide will continue until progression or up to 24 cycles. **Evaluation** (L: Laboratory testing, PE: physical examination) **PE/L**: physical examination on day 28 of every cycle and at study discontinuation. Laboratory blood testing weekly during radiation and every cycle thereafter. **MRI**: baseline screening within 21 days of day 1; then at day 56; then every 2 cycles (56 days +/− 3 days)

**Figure 2a.**
Median progression-free survival (PFS) curves for all patients and patients with methylated and unmethylated *MGMT* status. *MGMT*+: methylated *MGMT*; *MGMT*−: unmethylated *MGMT*

**Figure 2b.**
Median overall survival (OS) curves for all patients and patients with methylated and unmethylated *MGMT* status. *MGMT*+: methylated *MGMT*; *MGMT*−: unmethylated *MGMT*

See this image and copyright information in PMC

References

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Phase 2 Study of Bortezomib Combined With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Safety and Efficacy Assessment

Affiliations

Phase 2 Study of Bortezomib Combined With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Safety and Efficacy Assessment

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Conflict of interest statement

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