The purpose of this study was to further evaluate the therapeutic efficacy of convection enhanced delivery (CED) of
carboplatin in combination with
radiotherapy for treatment of the F98 rat
glioma.
Tumor cells were implanted stereotactically into the brains of syngeneic Fischer rats, and 13 or 17 d. later
carboplatin (20 μg/10 μl) was administered by either CED over 30 min or by Alzet osmotic pumps (0.5 μg/μl/h for 168 h.) beginning at 7 d after
tumor implantation. Rats were irradiated with a 15 Gy fractionated dose (5 Gy × 3) of 6 MV photons to the whole brain beginning on the day after
drug administration. Other groups of rats received either
carboplatin or X-irradiation alone. The
tumor carboplatin concentration following CED of 20 μg in 10 μl was 10.4 μg/g, which was equal to that observed following i.v. administration of 100 mg/kg b.w. Rats bearing small
tumors, treated with
carboplatin and X-irradiation, had a mean survival time (MST) of 83.4 d following CED and 111.8 d following pump delivery with 40% of the latter surviving >180 d (i.e. cured) compared to 55.2 d for CED and 77.2 d. for pump delivery of
carboplatin alone and 31.8 d and 24.2 d, respectively, for X-irradiated and untreated controls. There was no microscopic evidence of
residual tumor in the brains of all long-term survivors. Not surprisingly, rats with large
tumors had much shorter MSTs. Only modest increases in MSTs were observed in animals that received either
oral administration or CED of
temozolomide plus X-irradiation (23.2 d and 29.3 d) compared to X-irradiation alone. The present survival data, and those previously reported by us, are among the best ever obtained with the F98
glioma model. Initially, they could provide a platform for a Phase I clinical trial to evaluate the safety and potential therapeutic efficacy of CED of
carboplatin in patients with recurrent
glioblastomas, and ultimately a Phase II trial of
carboplatin in combination with
radiation therapy.