Publications [#98424] of John H Sampson

Papers Published

1. AB Heimberger, GE Archer, RE McLendon, C Hulette, AH Friedman, HS Friedman, DD Bigner, JH Sampson, Temozolomide delivered by intracerebral microinfusion is safe and efficacious against malignant gliomas in rats., Clinical cancer research : an official journal of the American Association for Cancer Research, UNITED STATES, vol. 6 no. 10 (October, 2000), pp. 4148-53, ISSN 1078-0432
   (last updated on 2006/06/06)

   Abstract:
   Intracerebral microinfusion (ICM) is an innovative technique of delivering therapeutic agents throughout large portions of the brain that circumvents the blood-brain barrier, minimizes systemic toxicity, and provides a homogeneous distribution of the infused agent. Temozolomide is a novel methylating agent with proven efficacy against malignant gliomas (MGs) after systemic administration but with dose-limiting myelotoxicity. Because MGs rarely metastasize, systemic drug delivery is unnecessary. Therefore, we evaluated the efficacy and toxicity of ICM with temozolomide in an athymic rat model of human MGs. Treatment of rats by ICM with temozolomide 3 days after intracerebral challenge with D54 human MG xenograft increased median survival by 128% compared with rats treated by ICM with saline, by 113% compared with rats treated with i.p. saline, and by 100% compared with rats treated with i.p. temozolomide (P < 0.001). Delay of treatment until 9 days after tumor challenge still resulted in a 23% increase in median survival in rats treated by ICM of temozolomide compared with rats treated with i.p. temozolomide. In addition, overall, 21.7% of rats treated by ICM with temozolomide survived for > 100 days without clinical or histological evidence of tumor. The dose of temozolomide delivered by ICM in this study was limited only by drug solubility, and no neurological or systemic toxicity could be attributed to ICM with temozolomide. Therefore, ICM of temozolomide may offer significant advantages in the treatment of MGs.

   Keywords:
   Animals • Antineoplastic Agents, Alkylating • Brain • Brain Neoplasms • Catheterization • Catheters, Indwelling* • Dacarbazine • Drug Delivery Systems* • Glioma • Humans • Male • Neoplasm Transplantation • Rats • Rats, Nude • Time Factors • Tumor Cells, Cultured • administration & dosage* • analogs & derivatives* • drug effects • drug therapy* • therapeutic use