Treatment > Capecitabine

Meeting Abstract

Low-dose chemotherapy in combination with COX-2 inhibitors and PPARgamma agonists in recurrent high-grade glioma - a phase-II study

U. Bogdahn, P. Hau, T. Jauch, U. Baumgart, O. Grauer, L. Kaes, H. Koch, C. Wismeth, P. Krauseneck, A. Steinbrecher

University of Regensburg, Regensburg, Germany; Nervenklinik Bamberg, Bamberg, Germany

Background. Peroxisome proliferator-activated receptors (PPAR) are overexpressed in about 50% of glioblastoma, possibly induce the expression of PTEN and have been shown to suppress neoangiogenesis.
The expression of COX (cyclooxygenase)-2 inhibitors correlates positively with tumor grade in patients with high-grade glioma (HGG).
Overexpression of COX-2 modulates immune responses, enhances proliferation and migration of glioma in vitro.
COX-2 inhibitors induce apoptosis and prevent neoangiogenesis.
Low-dose chemotherapy inhibits neoangiogenesis in HGG by induction of apoptosis in endothelial cells.
The combination of all three principles has been shown to induce a number of important mechanisms preventing the progression of HGG.

Methods. In this phase-II pilot trial, a combination regimen of Capecitabine (Xeloda) 2 x 1250 mg/m2 OD day 1-21 in 28 days, Pioglitazone (Actos) 60 mg OD and Refocoxib (Vioxx) 25 mg OD is used.
Twenty patients with histologically proven HGG will be included in first or second recurrence after standard therapy.
Primary endpoint is progression free survival, secondary endpoints are response rate, overall survival, toxicity and quality of life.

Results. As of end of november 2002, 7 patients with glioblastoma (GBM) have been included.
One additional patient was excluded after reference histology (oligoastrocytoma (OA) WHO grade II) and was treated as observation patient.
Toxicity was mild with palmaroplantar erythema (NCI-CTC grade III) in one patient.
One patient with GBM and the observation patient had partial responses (PR) lasting at least 8 weeks.
All other patients had tumor progression.

Discussion. A combination therapy with capecitabine, pioglitazone and refocoxib did induce objective responses in one patient with a slowly progressing GBM and one additional observation patient with OA WHO grade II.
Therefore, we assume that this approach may be more feasible for slowly progressing tumors, what would fit with the postulated mechanisms of the drugs used.
A completion of our trial and further studies will be necessary to draw final conclusions.

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