Therapeutic activity of the topoisomerase I inhibitor J-107088 [6-N-(1-hydroxymethyla-2-hydroxy) ethylamino-12,13-dihydro-13-(beta-D-gluco pyranosyl)5H-indolo[2,3-a]-pyrrolo[3,4-c]-carbazole-5,7(6H)-dione] against pediatric and adult central nervous system tumor xenografts

Purpose: The in vivo antitumor activity of a novel topoisomerase I inhibito r, J-107088, was tested in athymic nude mice bearing subcutaneous or intrac ranial pediatric and adult malignant CNS tumor-derived xenografts. Methods: J-107088 was administered to animals on days 1-5 and 8-12 via intraperiton eal injection at a dose of 54 mg/kg (162 mg/m(2)) per day in 10% dimethyl s ulfoxide in 0.9% saline. The xenografts evaluated were derived from a child hood glioblastoma multiforme (D-456 MG), a childhood medulloblastoma (D-341 MED), an adult anaplastic astrocytoma (D-54 MG), an adult glioblastoma mul tiforme (D-245 MG), and a procarbazine-resistant subline of D-245 MG [D-245 MG (PR)]. Results: J-107088 produced regressions and significant growth in hibition in all five of the xenograft lines growing subcutaneously. Growth delays ranged from 7.6 days with D-245 MG to 62.1 days with D-456 MG (P < 0 .001). J-107088 also produced an 83% increase in survival in mice bearing i ntracranial D-456 MG (P < 0.001). Conclusion: These results indicate that J -107088 may be active in the treatment of childhood and adult malignant bra in tumors and provide the rationale for initiation of clinical trials with this agent.