Enhanced survival and cure of F98 glioma-bearing rats following intracerebral delivery of carboplatin in combination with photon irradiation.
OBJECTIVE
The goal of the present study was to evaluate the efficacy of intracerebral (i.c.) administration of carboplatin by means of convection-enhanced delivery (CED) in combination with fractionated, external beam photon irradiation for the treatment of F98 glioma-bearing rats.


METHODS
Carboplatin (20 microg/20 microL) was administrated i.c. by CED to F98 glioma-bearing rats, 13 days after stereotactic implantation of 10(3) tumor cells. One day following initiation of CED, a 24-Gy X-ray dose was administered in three daily fractions of 8 Gy each. Photon irradiation was carried out using either a conventional (6 MV) linear accelerator or a monochromatic synchrotron source (80 keV) at the European Synchrotron Radiation Facility. The primary end point of this study was overall survival.


RESULTS
The median survival times were 79 and 60 days and the corresponding percent increase in life spans were 182% and 114%, respectively, for the combination of carboplatin chemotherapy and irradiation with either 6-MV or 80-keV photons. A subset of long-term survivors (>200 days) were observed in both chemoradiotherapy groups: 16.6% and 8.3% for 6 MV and 80 keV, respectively. In contrast, the median survival times for 6-MV or 80-keV irradiated controls, chemotherapy alone, and untreated controls were 42, 51, 45, and 28 days, respectively.


CONCLUSIONS
Our results convincingly show the therapeutic efficacy of i.c. administration of carboplatin by means of CED in combination with either 6-MV or 80-keV photons. Further studies are warranted to optimize this combination of chemoradiotherapy for malignant gliomas.
Rousseau
Julia
J
Equipe 6, Institut National de la Santé et de la Recherche Médicale U836, France.
Boudou
Caroline
C
Barth
Rolf F
RF
Balosso
Jacques
J
Estève
François
F
Elleaume
Hélène
H
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D017785:Photons / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D016190:Carboplatin