Biomaterial Database

Phase 2 study of BCNU and temozolomide for recurrent glioblastoma multiforme: North American Brain Tumor Consortium study. 2004

Michael D Prados, and W K Alfred Yung, and Howard A Fine, and Harry S Greenberg, and Larry Junck, and Susan M Chang, and M Kelly Nicholas, and H Ian Robins, and Minesh P Mehta, and Karen L Fink, and Kurt A Jaeckle, and John Kuhn, and Kenneth R Hess, and S Clifford Schold, and

Department of Neurological Surgery, University of California at San Francisco, San Francisco, CA 94143, USA. pradosm@neurosurg.ucsf.edu

The purpose of this study was to evaluate the activity, measured in terms of progression-free survival (PFS) and response rates, of 1,3-bis(chloro-ethyl)-1-nitrosourea (BCNU) plus temozolomide in adult patients with recurrent glioblastoma multiforme. The phase 2 dose and schedule for this trial was BCNU 150 mg/m(2) i.v. followed in 2 h by temozolomide 550 mg/m(2) as a single oral dose. Treatment was repeated every 6 weeks for up to 8 cycles unless tumor progression was documented. The primary end point was PFS at 6 months (PFS-6). Response was a secondary end point, measured by MR imaging, neurological status, and steroid requirements prior to each 6-week cycle. The median age of eligible patients was 53, and 89.5% had no prior chemotherapy. All patients were evaluable for toxicity and time to progression. The PFS-6 was 21%. Overall survival was 68% at 6 months and 26% at 1 year. The MRI response for 36 patients was 2 partial responses, 2 minor responses, 19 cases of stable disease, and 13 immediate progressions. Median survival was 34 weeks, and median PFS was 11 weeks. Toxicity was primarily myelosuppression; no toxic deaths occurred. Historical phase 2 study data in this patient population show a PFS-6 of 15%. Recent data for use of temozolomide alone have shown a PFS-6 of 21%. We conclude that BCNU plus temozolomide when used in these doses and schedule has only modest activity, with significant toxicity, and appears to be no more effective than single-agent temozolomide.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009364	Neoplasm Recurrence, Local	The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site.	Local Neoplasm Recurrence,Local Neoplasm Recurrences,Locoregional Neoplasm Recurrence,Neoplasm Recurrence, Locoregional,Neoplasm Recurrences, Local,Recurrence, Local Neoplasm,Recurrence, Locoregional Neoplasm,Recurrences, Local Neoplasm,Locoregional Neoplasm Recurrences,Neoplasm Recurrences, Locoregional,Recurrences, Locoregional Neoplasm
D009656	North America	The northern continent of the Western Hemisphere, extending northward from the Colombia-Panama border and including CENTRAL AMERICA, MEXICO, Caribbean area, the UNITED STATES, CANADA and GREENLAND. The term often refers more narrowly to MEXICO, continental UNITED STATES, AND CANADA.	Northern America
D001932	Brain Neoplasms	Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.	Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D002330	Carmustine	A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)	BCNU,1,3-Bis(2-Chloroethyl)-1-Nitrosourea,BiCNU,FIVB,N,N'-Bis(2-Chloroethyl)-N-Nitrosourea,Nitrumon
D003606	Dacarbazine	An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)	DTIC,5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide,Biocarbazine,DIC,DTIC-Dome,Decarbazine,Deticene,Dimethyl Imidazole Carboxamide,Dimethyl Triazeno Imidazole Carboxamide,ICDT,NSC-45388,Carboxamide, Dimethyl Imidazole,DTIC Dome,DTICDome,Imidazole Carboxamide, Dimethyl,NSC 45388,NSC45388
D005260	Female		Females
D005909	Glioblastoma	A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.	Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man