How effective is BCNU in recurrent glioblastoma in the modern era?
A phase II trial
Abstract
Background: The initial studies on nitrosoureas were performed >30 years ago. These drugs remain the standard chemotherapy for glioblastoma. However, because the criteria used to evaluate the activity of nitrosoureas in a neuro-oncologic setting have changed, new data on their activity are needed.
Methods: The authors conducted a phase II study on 40 patients with recurrent glioblastoma following surgery and standard radiotherapy. They analyzed progression-free survival at 6 months (PFS-6), time to progression (TTP), response rate, and toxicity. Patients were treated with 80 mg/m2 carmustine on days 1 to 3, every 8 weeks for a maximum of six cycles.
Results: Median TTP was 13.3 weeks (95% CI, 10.26 to 16.86 weeks), and PFS-6 was 17.5% (95% CI, 8.9 to 34.3). Response to chemotherapy, age ≤40 years, and performance status ≥90 were significant prognostic factors for TTP; however, with multivariate analysis, only response to chemotherapy was significant. The major side effects were reversible hematologic and long-lasting hepatic and pulmonary toxicity.
Conclusion: The activity of this BCNU regimen is comparable with that reported in the past and with the newest therapies, such as temozolomide. However, BCNU toxicity is high and recovery is slow, thus compromising the administration of further drugs in patients with progressive disease.
Get full access to this article
View all available purchase options and get full access to this article.
References
1.
Surawicz TS, Davis F, Freels S, Laws ER Jr, Menck HR. Brain tumor survival: results from the National Cancer Data Base. J Neurooncol. 1998; 40: 151–160.
2.
Brandes AA, Fiorentino M. The role of chemotherapy in recurrent gliomas: an overview. Cancer Invest. 1996; 14: 547–555.
3.
Brandes AA, Lacombe D, Vecht C. Future trends in the treatment of brain tumors. Eur J Cancer. 2001; 37: 2297–2301.
4.
Kleihues P, Louis DN, Scheithauer BW, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol. 2002; 3: 215–225.
5.
World Health Organization: WHO Handbook for reporting results of cancer treatment (WHO offset Publications n°48). Neoplasma. 1980; 20: 37–46.
6.
Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG. Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol. 1990; 8: 1277–1280.
7.
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989; 10: 1–10.
8.
Kaplan EL, Meier P. Non parametric estimation for incomplete observation. J Am Stat Assoc. 1958; 53: 457–481.
9.
Cox DR. Regression models and life tables. J R Stat Soc. 1972; 34: 187–202.
10.
Wong ET, Hess KR, Gleason MJ, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled into phase II clinical trials. J Clin Oncol. 1999; 17: 2572–2578.
11.
Yung A, Albright R, Olson J, et al. A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer. 2000; 83: 588–593.
12.
Brada M, Hoang-Xuan K, Rampling R, et al. Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse. Ann Oncol. 2001; 12: 259–266.
13.
Chang SM, Theodosopoulos P, Lamborn K, et al. Temozolomide in the treatment of recurrent malignant glioma. Cancer. 2004; 100: 605–611.
14.
Fine HA, Wen PJ, Maher EA, et al. Phase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas. J Clin Oncol. 2003; 21: 2299–2304.
15.
Brandes AA, Basso U, Reni M, et al. First line chemotherapy with cisplatin plus fractionated temozolomide in recurrent glioblastoma multiforme: a phase II study of Gruppo Italiano Cooperativo di Neuro-oncologia (GICNO). J Clin Oncol. 2004; 22: 1598–1604.
16.
Dropcho EJ, Soong SJ. The prognostic impact of prior low grade histology in patients with anaplastic gliomas: a case control study. Neurology. 1996; 47: 684–690.
17.
Winger MJ, Macdonald DR, Cairncross JG. Supratentorial anaplastic gliomas in adults. The prognostic importance of extent of resection and prior low grade glioma. J Neurosurg. 1989; 71: 487–493.
18.
Brandes AA, Ermani M, Basso U, et al. Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: a phase II study. Ann Oncol. 2001; 12: 255–7.
19.
Rich JN, Reardon DA, Peery T, et al. Phase II trial of gefitinib in recurrent glioblastoma. J Clin Oncol. 2004; 22: 133–142.
20.
Groves MD, Puduvalli VK, Hess KR, et al. Phase II trial of temozolomide plus matrix metalloproteinase inhibitor, marimastat, in recurrent and progressive glioblastoma multiforme. J Clin Oncol. 2002; 20: 1383–1388.
21.
Jaeckle KA, Hess KR, Yung A, et al. Phase II evaluation of temozolomide and 13-cis retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium Study. J Clin Oncol. 2003; 21: 2305–2311.
Information & Authors
Information
Published In
Copyright
© 2004.
Publication History
Received: March 30, 2004
Accepted: June 2, 2004
Published online: October 11, 2004
Published in issue: October 12, 2004
Authors
Metrics & Citations
Metrics
Citation information is sourced from Crossref Cited-by service.
Citations
Download Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.
Cited By
- Emerging Approaches in Glioblastoma Treatment: Modulating the Extracellular Matrix Through Nanotechnology, Pharmaceutics, 17, 2, (142), (2025).https://doi.org/10.3390/pharmaceutics17020142
- Regorafenib Treatment for Recurrent Glioblastoma Beyond Bevacizumab-Based Therapy: A Large, Multicenter, Real-Life Study, Cancers, 17, 1, (46), (2024).https://doi.org/10.3390/cancers17010046
- Nanoparticle-Based Treatment and Imaging of Brain Tumors Potentials and Limitations, The Textbook of Nanoneuroscience and Nanoneurosurgery, (391-407), (2024).https://doi.org/10.1007/978-3-030-80662-0_23
- Current and Future Drugs for Brain Tumors Treatment, Advanced Imaging and Therapy in Neuro-Oncology, (83-99), (2024).https://doi.org/10.1007/978-3-031-59341-3_6
- Targeting drug resistance in glioblastoma (Review), International Journal of Oncology, 65, 2, (2024).https://doi.org/10.3892/ijo.2024.5668
- Current and promising treatment strategies in glioma, Reviews in the Neurosciences, 34, 5, (483-516), (2022).https://doi.org/10.1515/revneuro-2022-0060
- Updates in the Management of Recurrent Glioblastoma Multiforme, Journal of Neurological Surgery Part A: Central European Neurosurgery, 84, 02, (174-187), (2022).https://doi.org/10.1055/s-0042-1749351
- Strained Ammonium Precursors for Radiofluorinations, ChemistryOpen, 11, 6, (2022).https://doi.org/10.1002/open.202200039
- A retrospective analysis of irinotecan and bevacizumab combination therapy in recurrent high-grade glioma and glioblastoma multiforme, International Journal of Neurooncology, 5, 1, (1-9), (2022).https://doi.org/10.4103/IJNO.IJNO_1_23
- Кармустин в терапии В-клеточных лимфомCarmustine in the Therapy of B-Cell Lymphomas, Clinical Oncohematology, 14, 4, (496-502), (2021).https://doi.org/10.21320/2500-2139-2021-14-4-496-502
- See more
Loading...
View Options
Login options
Check if you have access through your login credentials or your institution to get full access on this article.
Personal login Institutional LoginPurchase Options
The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.
If you need immediate support or to place an order, please call or email customer service:
- 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
- 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
- [email protected]
We appreciate your patience during this time and apologize for any inconvenience.