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Phase 2 study of BCNU and temozolomide for
recurrent glioblastoma multiforme: North American Brain Tumor Consortium study
Michael D. Prados, W.K. Alfred Yung, Howard A. Fine, Harry S. Greenberg,
Larry Junck, Susan M. Chang, M. Kelly Nicholas, H. Ian Robins, Minesh P. Mehta,
Karen L. Fink, Kurt A. Jaeckle, John Kuhn, Kenneth R. Hess, and S. Clifford
Schold Jr.
Departments of Neurological Surgery [M.D.P., S.M.C.] and
Neuro-Oncology [M.K.N.], University of California at San Francisco, San
Francisco, CA 94143; Departments of Neuro-Oncology [W.K.A.Y.] and Biostatistics
[K.R.H.], The University of Texas M.D. Anderson Cancer Center, Houston, TX
77030; Neuro-Oncology Branch, National Cancer Institute, Bethesda, MD 20892 [H.A.F.]; Department of Neurology, University of Michigan, Ann Arbor, MI 48109
[H.S.G., L.J.]; Departments of Medicine [H.I.R.] and Radiotherapy [M.P.M.],
University of Wisconsin, Madison, WI 53792; Department of Neurology, The
University of Texas Southwestern Medical Center, Dallas, TX 75390 [K.L.F.];
Departments of Neurology and Hematology/Oncology, Mayo Clinic Jacksonville,
Jacksonville, FL 32224 [K.A.J.]; College of Pharmacy, University of Texas Health
Science Center at San Antonio, San Antonio, TX 78229 [J.K.]; Office of Clinical
Research, University of Pittsburgh, Pittsburgh, PA 15261 [S.C.S.]; USA.
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/m2 i.v.
followed in 2 h by temozolomide 550 mg/m2 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.
© 2003 Duke University Press
Source: http://juno.ingentaselect.com/cgi-bin/linker?ini=dup_no&reqidx=/cw/dup/15228517/v6n1/s6/p33
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