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Phase
1 trial of irinotecan plus BCNU in patients with progressive or recurrent
malignant glioma
Jennifer
A. Quinn, David A. Reardon, Allan H. Friedman, Jeremy N. Rich, John H. Sampson,
James Vredenburgh, Sridharan Gururangan, James M. Provenzale, Amy Walker, Holly
Schweitzer, Darell D. Bigner, Sandra Tourt-Uhlig, James E. Herndon II, Mary Lou
Affronti, Susanne Jackson, Deborah Allen, Karen Ziegler, Cindy Bohlin, Christy
Lentz, Henry S. Friedman
Departments of Surgery (J.A.Q., D.A.R., A.H.F., J.N.R., J.H.S., J.V., S.G., A.W., H.S., D.D.B.,
S.T.-U., M.L.A., S.J., D.A., K.Z., C.B., C.L., H.S.F.), Radiology (J.M.P.),
Pathology (D.D.B), and Biostatistics and Bioinformatics (J.E.H.), Duke
University Medical Center, Durham, NC 27710 USA.
Irinotecan
is a topoisomerase I inhibitor previously shown to be active in the treatment of
malignant glioma.
We now report the results of a phase 1 trial of irinotecan plus BCNU, or
1,3-bis(2-chloroethyl)-1-nitrosourea, for patients with recurrent or progressive
M G.
Irinotecan dose escalation occurred independently within 2 strata: patients
receiving enzyme-inducing antiepileptic drugs (EIAEDs) and patients not
receiving EIAEDs.
BCNU was administered at a dose of 100 mg/m2 over 1 h every 6 weeks
on the same day as the first irinotecan dose was administered.
Irinotecan was administered intravenously over 90 min once weekly.
Treatment cycles consisted of 4 weekly administrations of irinotecan followed by
a 2-week rest with dose escalation in cohorts of 3 to 6 patients.
Seventy-three patients were treated, including 49 patients who were on EIAEDs
and 24 who were not on EIAEDs.
The maximum tolerated dose for patients not on EIAEDs was 125 mg/m2.
The maximum tolerated dose for patients on EIAEDs was 225 mg/m2.
Dose-limiting toxicity was evenly distributed among the following organ systems:
pulmonary, gastrointestinal, cardiovascular, neurologic, infectious, and
hematologic, without a clear predominance of toxicity involving any one organ
system.
There was no evidence of increasing incidence of toxicity involving one organ
system as irinotecan dose was escalated.
On the basis of these results, we conclude that the recommended doses of
irinotecan for a phase 2 clinical trial when given in combination with BCNU (100
mg/m2) are 225 mg/m2 for patients on EIAEDs and 125 mg/m2
for patients not on EIAEDs.
© 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/s8/p145
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