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Prolonged
infusional topotecan and accelerated hyperfractionated 3d-conformal radiation in
patients with newly diagnosed glioblastoma--a phase I study
Grabenbauer
GG, Anders K, Fietkau RJ, Klautke G, Feldmann HJ, Weiser S, Staab HJ, Krauseneck
P, Sauer R
Department
of Radiation Oncology, University Hospitals of Erlangen-Nurnberg, Erlangen,
Germany.
gerd.grabenbauer@strahlen.imed.uni-erlangen.de
Purpose.
Topotecan has demonstrated exceptional central nervous system penetration as
well as radiosensitizing properties in glioblastoma xenografts [Chastagner et
al., Int J Radiat Oncol Biol Phy 50: 777-782, 2001].
This phase I trial was
performed to determine the maximum tolerated dose and the recommended dose of
topotecan continuous infusion administered together with concomitant
radiotherapy in patients with glioblastoma.
Patients and
Methods. A total of 20
patients were treated in this trial.
Twenty one day topotecan continuous
infusion was escalated from 0.3 mg/m2/d in increments of 0.1 mg/m2/d and cohorts
of 3-6 patients until maximum tolerated dose was reached; Three-dimensional (3d)
conformal radiotherapy was applied concurrently twice daily with a fraction size
of 1.75 Gy up to 57.75 Gy total dose.
Three additional cycles of maintenance
topotecan chemotherapy were scheduled.
Results. Fifty-three courses were
performed in 5 dose levels (0.3 mg/m2/d: 12 cycles, 0.4 mg/m2/d: 6 cycles, 0.5
mg/m2/d: 10 cycles, 0.6 mg/m2/d: 6 cycles, 0.7 mg/m2/d: 19 cycles).
Maximum
tolerated dose was reached at dose level 5 (0.7 mg/m2/d), because 3/7 patients
suffered from dose limiting toxicity.
These were febrile sinusitis, bacterial
sepsis and grade 4 thrombocytopenia.
Neutropenia of grade 4 was encountered in 2
cycles (0.5 and 0.7 mg/m2/d).
Response data were available in 17 patients, 3 of
which (18%) achieved partial remission, 12 (71%) stable disease throughout the
observation period and 2 (11%) progressive disease.
Conclusion. The recommended
dose for further trials will be 0.6 mg/m2/d topotecan administered as 21 days
continuous infusion in combination with accelerated 3d conformal radiation.
PMID: 12510778 [PubMed - in process]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12510778&dopt=Abstract
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