Preclinical ReportResponse of short-term cultures derived from human malignant glioma to aziridinylbenzoquinone, etoposide and doxorubicin: an in vitro phase II trialDarling, John L1; Thomas, David GT1Author Information 1University Department of Neurosurgery, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK. Correspondence to JL Darling, University Department of Neurosurgery, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. Tel: (+44) 20 7837 3611; Fax: (+44) 20 7278 7894; e-mail: J.Darling@ion.ucl.ac.uk This study was supported in part by grants from the Cancer Research Campaign and the Brain Research Trust, London. (Received 16 July 2001; revised form accepted 31 July 2001) Anti-Cancer Drugs: October 2001 - Volume 12 - Issue 9 - p 753-760 Buy Abstract The relative resistance of malignant glioma to chemotherapy makes the identification of new cytotoxic drugs critically important. The use of short-term cultures derived from these tumors to screen drugs at doses that can be attained within human intracranial tumors provides a model system that should be capable of identifying effective drugs suitable for clinical evaluation. The sensitivity of a panel of short-term cultures derived from 22 malignant astrocytoma and four malignant oligodendroglioma was assessed to aziridinylbenzoquinone (AZQ), etoposide and doxorubicin (DOX) using a [35S]methione uptake assay. The ID50 of each culture was compared to the levels of drug which could be achieved in the tumor using standard doses. There was marked heterogeneity between cultures in response to each drug. Whilst there was no evidence that cultures derived from grade III astrocytoma were more sensitive to any of the drugs than cultures derived from grade IV astrocytoma, cultures derived from oligodendroglioma tended to be more sensitive to the alkylating agent AZQ, but not to either of the other drugs. The sensitivity of these short-term cultures at concentrations that can be achieved in situ corresponded well with the clinical efficacy of AZQ and etoposide. Although DOX appeared to be toxic to human gliomas cells in vitro, its limited penetration into the intact brain would seem to preclude its use i.v., but it is likely to be effective if local drug delivery techniques could be employed. The study suggests that short-term cultures derived from malignant glioma should be used to screen investigational agents for potential clinical efficacy. © 2001 Lippincott Williams & Wilkins, Inc.