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A phase II trial of
conventional radiation therapy (XRT) plus high dose tamoxifen (TAM) for the
treatment of supratentorial glioblastoma multiforme (GBM): RTOG protocol BR-0021
H. I. Robins, M. Won, C. Schultz, A. Choucair, D. Brachman, W. Demas, M.
Mehta
UWCCC, Madison, WI; RTOG, Philadelphia, PA; Medical College of
Wisconsin, Milwaukee, WI; LDS Hospital, Salt Lake City, UT; Foundation for
Cancer Research and Education, Phoenix, AZ; Summa Health Systems, Akron, OH.
Background. Preclinical studies support the
concept that inhibition of protein kinase C (PKC) by TAM should provide both
anti-neoplastic effects and radiosensitization.
Methods.
High dose TAM (80 mg/m2 PO daily in divided doses) was given with and
after conventional XRT to inhibit PKC mediated signaling, which is known to be
enhanced in GBM.
Patients (n=77) were accrued between 12/00-12/01; 75 patients were
analyzable.
Pretreatment characteristics included: 52%<60 years of age; 39% had a Zubrod
score of 0, 70% had minor or no neurological symptoms; 65% were RTOG
–recursive partition analysis (RPA) class III & IV.
Results. A
sample of 46 patients was reviewed for TAM delivery; 78% achieved acceptable
dosing.
Notable toxicity included: Late radiation Grade (G) G3 =2; Thrombo-embolic
disease G2=2, G3=8, G4=3, G5=1 for an incidence of 18.7%, (which is lower than
expected, based on the literature for DVT in GBM patients not receiving
TAM).
Median survival time (MST) was 9.7 months (M).
This result was compared (using 3 different statistical methodologies) to the
historical GBM control database of 1443 drug / XRT treated patients RPA class
III, IV, & V.
After controlling for RPA class IV, the MST was 11.3M, which compares to the
historical RPA control of 11.2 M (p=0.38).
Conclusions.
1) The results obtained do not exhibit a substantial advance over previous
studies with various XRT/drug doublets including BCNU.
As TAM does not have significant overlapping toxicities with most other drugs,
its testing in a combined modality approach with other medications may be
justified in future clinical trails.
2) Historically the incidence of thrombo-embolic events in GBM patients is
~30%.
The lower than expected incidence seen here has also been observed in other high
dose TAM GBM studies.
We speculate that TAM inhibited the PKC mediated phosphorylation of coagulation
factors.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-001267,00.asp
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