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Phase
2 trial of BCNU plus irinotecan in adults with malignant glioma
David
A. Reardon, Jennifer A. Quinn, Jeremy N. Rich, Sridharan Gururangan, James
Vredenburgh, John H. Sampson, James M. Provenzale, Amy Walker, Michael
Badruddoja, Sandra Tourt-Uhlig, James E. Herndon II, Jeannette M. Dowell, Mary
Lou Affronti, Susanne Jackson, Deborah Allen, Karen Ziegler, Steven Silverman,
Cindy Bohlin, Allan H. Friedman, Darell D. Bigner, Henry S. Friedman
Departments of Surgery (D.A.R., J.A.Q., J.N.R., S.G., J.V.,
J.H.S., A.W., M.B., S.T.-U., M.L.A., S.J., D.A., K.Z., S.S., C.B., A.H.F.,
D.D.B., H.S.F.), Neurology (J.A.Q., J.N.R.), Pediatrics (D.A.R., S.G., H.S.F.),
Radiology (J.M.P.), Cancer Center Biostatistics (J.E.H., J.M.D.), and Pathology
(D.D.B.), Duke University Medical Center, Durham, NC 27710, USA
In
preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)1-nitrosourea, plus CPT-11
(irinotecan) exhibits scheduledependent, synergistic activity against malignant
glioma (MG).
We previously established the maximum tolerated dose of CPT-11 when administered
for 4 consecutive weeks in combination with BCNU administered on the first day
of each 6-week cycle.
We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG.
In the current study, BCNU (100 mg/m2) was administered on day 1 of
each 6-week cycle.
CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for
patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2
for those not on these medications.
Newly diagnosed patients received up to 3 cycles before radiotherapy, while
recurrent patients received up to 8 cycles.
The primary end point of this study was radiographic response, while time to
progression and overall survival were also assessed.
Seventy-six patients were treated, including 37 with newly diagnosed tumors and
39 with recurrent disease.
Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had
anaplastic oligodendroglioma.
Toxicities (grade ≥ 3) included infections (13% ), thromboses (12%),
diarrhea (10% ), and neutropenia (7%).
Interstitial pneumonitis developed in 4 patients.
Five newly diagnosed patients (14%; 95% CI, 5%-29%) achieved a radiographic
response (1 complete response and 4 partial responses).
Five patients with recurrent MG also achieved a response (1 complete response
and 4 partial responses; 13%; 95% CI, 4%-27%).
More than 40% of both newly diagnosed and recurrent patients achieved stable
disease.
Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme
patients and 16.9 weeks for recurrent anaplastic astrocytoma/anaplastic
oligodendroglioma patients.
We conclude that the activity of BCNU plus CPT-11 for patients with MG appears
comparable to that of CPT-11 alone and may be more toxic.
© 2003 Duke
University Press
Source: http://konstanza.ingentaselect.com/vl=1635347/cl=66/nw=1/rpsv/cgi-bin/linker?ini=dup_no&reqidx=/cw/dup/15228517/v6n2/s7/p134
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