Therapeutic activity of the topoisomerase I inhibitor J-107088 [6-N-(1-hydroxymethyla-2-hydroxy) ethylamino-12,13-dihydro-13-(β-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

• Published in: Cancer chemotherapy and pharmacology 2001-09, Vol.48 (3), p.250-254
• Main Authors: CAVAZOS, Christina M, KEIR, Stephen T, YOSHINARI, Tomoko, BIGNER, Darell D, FRIEDMAN, Henry S
• Format: Article
• Language: English
• Subjects: Adult; Animals; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Brain Neoplasms - drug therapy; Carbazoles - therapeutic use; Chemotherapy; Child; Enzyme Inhibitors - therapeutic use; Female; Glioma - drug therapy; Glucosides - therapeutic use; Humans; Indoles; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Medical sciences; Mice; Mice, Nude; Neoplasm Transplantation; Pharmacology. Drug treatments; Survival Rate; Topoisomerase I Inhibitors; Transplantation, Heterologous; Treatment Outcome; Tumor Cells, Cultured
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s002800100347

The in vivo antitumor activity of a novel topoisomerase I inhibitor, J-107088, was tested in athymic nude mice bearing subcutaneous or intracranial pediatric and adult malignant CNS tumor-derived xenografts. J-107088 was administered to animals on days 1-5 and 8-12 via intraperitoneal injection at a dose of 54 mg/kg (162 mg/m2) per day in 10% dimethyl sulfoxide in 0.9% saline. The xenografts evaluated were derived from a childhood glioblastoma multiforme (D-456 MG), a childhood medulloblastoma (D-341 MED), an adult anaplastic astrocytoma (D-54 MG), an adult glioblastoma multiforme (D-245 MG), and a procarbazine-resistant subline of D-245 MG [D-245 MG (PR)]. J-107088 produced regressions and significant growth inhibition 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 intracranial D-456 MG (P < 0.001). These results indicate that J-107088 may be active in the treatment of childhood and adult malignant brain tumors and provide the rationale for initiation of clinical trials with this agent.