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The
treatment of newly diagnosed glioblastoma multiforme using high dose tamoxifen (TMX),
radiotherapy and convenzional chemotherapy
Vertosick,
F.T., and Selker, R.G.
The
Center for Neuro-oncology, The Western Pennsylvania Hospital, Pittsburg, PA
15224 USA
Standard
therapy of glioblastoma multiforme (GBM) consists of external radiotherapy +
chemotherapy; median survivals are typically less then 52 weeks.
Tamoxifen (TMX) inhibits GBM cell lines in culture at high concentrations (1 uM)
This concentration can be obtained in vivo when high doses of TMX
(200-500 mg/day) are given for extended periods.
Sporadic
reports on dramatic GBM regression using high doses have appeared.
We treated a pilot group of 23 GBM patients using standard therapy + 240 mg TMX/day.
TMX was started after diagnosis and before radiotherapy in most patients, and
continued until death.
Nausea forced dose-reduction in most patients, but all had at least four weeks
on the highest dose.
Patients
characteristics: 11M, 12F; mean age: 54 years; mean Karnofsky: 80; alive/dead:
9/14; mean time on TMX: 43 weeks.
Median survival from diagnosis: 69.3 weeks (mean: 85.8
weeks).
Median
survival from initiation of TMX: 66.1 weeks (mean: 82.2 weeks).
Survival fractions: 0.91 at 26 weeks, 0.65 at 52 weeks, 0.45 at 104 weeks, 0.24
at 182 weeks.
One patient is alive and well at 206 weeks.
Three patients had complete resolution of enhancement on CT.
One patient had visual blurring which responded to dose reduction; otherwise
there were no serious side-effects attributed to the drug save for nausea.
The
chief drawback to this therapy in the United States is cost.
These results suggest that a larger trial of high dose TMX as part of the
initial management of GBM is warranted.
Source: Proceedings
of the American Association for Cancer Research, Volume
38, March 1997, Page 431
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