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Topotecan can compensate for protracted radiation
treatment time effects in high grade glioma xenografts (bigstar)
Pinel
S, Chastagner
P, Merlin
JL, Marchal
C, Taghian
A, Barberi-Heyob
M
Laboratoire de Recherche en Oncologie, Centre A. Vautrin,
Vandoeuvre-les-Nancy, France, pinel.sophie@tiscali.fr.
Purpose. Several studies reported that prolongation of overall treatment
time of fractionated radiotherapy reduces the chance of tumor control.
In
the present study, we hypothesize that combining topotecan with irradiation
could compensate for this detrimental time effect on the radioresponse.
Therefore, we investigated the efficiency of different schedules of
topotecan (TPT), radiotherapy (RT) or concomitant combination TPT + RT.
Methods and Materials. Experiments were performed in two human high-grade
glioma xenograft models (U87 and GBM Nan1).
TPT and RT were delivered at a
total dose of 3 mg/kg and 40 Gy, respectively.
For the TPT + RT groups, TPT
was injected 5 min before radiation.
Total radiation doses were delivered in
5, 10, 20, or 30 fractions over 1, 2, 4, or 6 weeks, respectively.
The
efficiency of TPT, RT, and TPT + RT was evaluated by tumor growth delay
(TGD).
Results. At this low total dose, and independent of the schedule, no
efficacy was found in TPT-treated glioma xenografts.
Conversely,
radiotherapy-induced antitumor effect decreased with prolongation of
treatment time.
For TPT + RT combination, antitumor activity was not
influenced by schedule, and tumor response was always comparable to those
measured for the shortest and the most efficient irradiation schedule (i.e.
1 week).
When treatment was delivered over 4 or 6 weeks in U87 glioma
xenografts, therapeutic enhancement ratios reached 2.6 and 3.7,
respectively.
This indicated that the interaction between ionizing radiation
and topotecan was synergistic.
Conclusion. The present study demonstrated
that concomitant topotecan can compensate for the detrimental effect of
treatment time protraction on radiotherapy efficacy in two malignant glioma
xenografts.
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