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Enhanced Survival and Cure of F98 Glioma–Bearing Rats following Intracerebral Delivery of Carboplatin in Combination with Photon Irradiation

Authors' Affiliations: ¹ Equipe 6, Institut National de la Santé et de la Recherche Médicale U836; ² Université Joseph Fourier; ³ Medical Beamline ID17, European Synchrotron Radiation Facility, Institut National de la Santé et de la Recherche Médicale Unité 836; ⁴ Centre Hospitalier Universitaire, Grenoble, France; and ⁵ Department of Pathology, The Ohio State University, Columbus, Ohio

Requests for reprints: Hélène Elleaume, Medical Beamline, European Synchrotron Radiation Facility, Institut National de la Santé et de la Recherche Médicale Unité 836, BP 220, 38043 Grenoble Cedex 9, France. Phone: 33-4-7688-2343; Fax: 33-4-7688-2885; E-mail: h.elleaume{at}esrf.fr.

Purpose: 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.

Experimental Design: Carboplatin (20 µg/20 µL) was administrated i.c. by CED to F98 glioma–bearing rats, 13 days after stereotactic implantation of 10³ 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.

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