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Convection enhanced delivery of carboplatin in combination with radiotherapy for the treatment of brain tumors

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
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An Erratum to this article was published on 31 July 2010

An Erratum to this article was published on 31 July 2010

Abstract

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.

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Acknowledgments

We thank Dr. Abhik Ray Chaudhury for reviewing selected histologic sections with one of us (RFB), Mr. Andrew Pultz, OSU James Cancer Hospital Outpatient Pharmacy for generously providing us with carboplatin, Mr. Shawn Scully for assistance in taking photomicrographs, Dr. Richard Hill for his comments relating to our in vitro studies, and finally Ms. Michelle Van Fossen for expert secretarial assistance in the preparation of this manuscript. Support for this study was generously provided by the Musella Foundation, the Grey Ribbon Crusade, the Have a Chance Foundation, The Brad Kaminsky Foundation, and The Ohio State University Department of Pathology.

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There are no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, The Ohio State University, 165 Hamilton Hall, 1645 Neil Avenue, Columbus, OH, 43210, USA

    Weilian Yang, Tianyao Huo & Rolf F. Barth

  2. Department of Radiation Oncology, The Ohio State University, 300 W 10th Ave, Columbus, OH, 43210, USA

    Nilendu Gupta, Michael Weldon & John C. Grecula

  3. Department of Radiology, University of Michigan, Ann Arbor, MI, 48109, USA

    Brian D. Ross & Benjamin A. Hoff

  4. Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY, 10021, USA

    Ting-Chao Chou

  5. INSERM, Institute of Neurosciences U836 Equipe 6, Grenoble, France

    Julia Rousseau & Hélène Elleaume

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  1. Weilian Yang
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Correspondence to Rolf F. Barth.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s11060-010-0316-4

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Yang, W., Huo, T., Barth, R.F. et al. Convection enhanced delivery of carboplatin in combination with radiotherapy for the treatment of brain tumors. J Neurooncol 101, 379–390 (2011). https://doi.org/10.1007/s11060-010-0272-z

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