Radiation therapy combined with intracerebral convection-enhanced delivery of cisplatin or carboplatin for treatment of the F98 rat glioma.

Abstract

The purpose of this review is to summarize our own experimental studies carried out over a 13-year period of time using the F98 rat glioma as model for high grade gliomas. We evaluated a binary chemo-radiotherapeutic modality that combines either cisplatin (CDDP) or carboplatin, administered intracerebrally (i.c.) by means of convection-enhanced delivery (CED) or osmotic pumps, in combination with either synchrotron or conventional X-irradiation. F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Approximately 14days later, either CDDP or carboplatin was administered i.c. by CED, followed 24h later by radiotherapy using either a synchrotron or, subsequently, megavoltage linear accelerators (LINAC). CDDP was administered at a dose of 3µg in 5 µL, followed 24h later with an irradiation dose of 15Gy or carboplatin at a dose of 20µg in 10 µL, followed 24h later with 3 fractions of 8Gy each, at the source at the European Synchrotron Radiation Facility (ESRF). This resulted in a median survival time (MeST) > 180days with 33% long term survivors (LTS) for CDDP and a MeST > 60days with 8 to 22% LTS, for carboplatin. Subsequently it became apparent that comparable survival data could be obtained with megavoltage X-irradiation using a LINAC source. The best survival data were obtained with a dose of 72µg of carboplatin administered by means of Alzet® osmotic pumps over 7days. This resulted in a MeST of > 180days, with 55% LTS. Histopathologic examination of all the brains of the surviving rats revealed no residual tumor cells or evidence of significant radiation related effects. The results obtained using this combination therapy has, to the best of our knowledge, yielded the most promising survival data ever reported using the F98 glioma model.