Extreme drug resistance in primary brain tumors: In vitro analysis of 64 resection specimens

Understanding chemoresistance profiles of brain tumors may aid in more educated selection of chemotherapeutic regimens for clinical trials and patient treatment. Although the literature contains many reports of the application of drug resistance assays, little is known about extreme drug resistance (EDR) in primary brain tumors. We undertook this study to determine chemoresistance profiles for brain tumors. From September 1991 to February 1998, we collected 64 brain tumor specimens from patients admitted to the Johns Hopkins Hospital. Tumors were classified according to the revised World Health Organization system. Brain tumor specimens were tested against 13 different chemotherapeutic agents using an extreme drug resistance assay. Results were reported as percent cell inhibition (PCI) (compared to control cultures). A drug resistance profile (extreme, intermediate, or low) was determined based on statistical comparison to a historical database of tumor specimens tested against the same panel of chemotherapeutic agents. Brain tumor specimens were classified histologically as Grade IV astrocytoma (glioblastoma multiforme, n = 35), Grade II/III astrocytoma (n = 11), oligodendroglioma (n = 6), meningioma (n = 9), hemangiopericytoma (n = 2), and ependymoma (n = 1). A large percentage of glioblastomas displayed extreme drug resistance to paclitaxel (69%, n = 35), SN38 (75%, n = 28), and vincristine (38%, n = 29). The majority of Grade II/III astrocytomas displayed extreme drug resistance to carboplatin (67%, n = 6), cisplatin (60%, n = 10), and paclitaxel (60%, n = 10). In a similar fashion, oligodendrogliomas displayed extreme drug resistance to vincristine (60%, n = 5) and paclitaxel (50% n = 6). Most meningiomas displayed extreme drug resistance to vincristine (75%, n = 8), dacarbazine (63%, n = 8), and 4-HC (50%, n = 8). Through the continued analysis of brain tumor specimens and compilation of data from multiple institutions, chemoresistance profiles could assist in the development of rationale clinical trials and treatment regimens for patients with brain tumors.