Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies
Abstract
Purpose: To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods: This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m{sup 2}/dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m{sup 2} starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributable to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non-dose-limiting toxicity, and treatment response. Results: A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m{sup 2}/dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patientsmore »
- Authors:
-
- Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA (United States)
- Genzyme Inc., Cambridge, MA (United States)
- Department of Medical Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA (United States)
- Department of Neurosurgery, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA (United States)
- Publication Date:
- OSTI Identifier:
- 21276819
- Resource Type:
- Journal Article
- Journal Name:
- International Journal of Radiation Oncology, Biology and Physics
- Additional Journal Information:
- Journal Volume: 74; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2008.08.050; PII: S0360-3016(08)03512-8; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 62 RADIOLOGY AND NUCLEAR MEDICINE; CENTRAL NERVOUS SYSTEM; ERYTHEMA; GLIOMAS; PATIENTS; RADIATION DOSES; RADIOTHERAPY; TOXICITY
Citation Formats
Kubicek, Gregory J, Werner-Wasik, Maria, Machtay, Mitchell, Mallon, Gayle, Myers, Thomas, Ramirez, Michael, Andrews, David, Curran, Walter J, and Dicker, Adam P. Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies. United States: N. p., 2009.
Web. doi:10.1016/j.ijrobp.2008.08.050.
Kubicek, Gregory J, Werner-Wasik, Maria, Machtay, Mitchell, Mallon, Gayle, Myers, Thomas, Ramirez, Michael, Andrews, David, Curran, Walter J, & Dicker, Adam P. Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies. United States. https://doi.org/10.1016/j.ijrobp.2008.08.050
Kubicek, Gregory J, Werner-Wasik, Maria, Machtay, Mitchell, Mallon, Gayle, Myers, Thomas, Ramirez, Michael, Andrews, David, Curran, Walter J, and Dicker, Adam P. 2009.
"Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies". United States. https://doi.org/10.1016/j.ijrobp.2008.08.050.
@article{osti_21276819,
title = {Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies},
author = {Kubicek, Gregory J and Werner-Wasik, Maria and Machtay, Mitchell and Mallon, Gayle and Myers, Thomas and Ramirez, Michael and Andrews, David and Curran, Walter J and Dicker, Adam P.},
abstractNote = {Purpose: To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods: This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m{sup 2}/dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m{sup 2} starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributable to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non-dose-limiting toxicity, and treatment response. Results: A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m{sup 2}/dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patients with high-grade glioma. Conclusion: Bortezomib administered at its typical 'systemic' dose (1.3 mg/m{sup 2}) is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies. A Phase II study to characterize efficacy is warranted.},
doi = {10.1016/j.ijrobp.2008.08.050},
url = {https://www.osti.gov/biblio/21276819},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 74,
place = {United States},
year = {Mon Jun 01 00:00:00 EDT 2009},
month = {Mon Jun 01 00:00:00 EDT 2009}
}