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

AbstractPURPOSE:
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.
METHODS:
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)].
RESULTS:
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).
CONCLUSION:
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.
AuthorsC M Cavazos, S T Keir, T Yoshinari, D D Bigner, H S Friedman
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 48 Issue 3 Pg. 250-4 (Sep 2001) ISSN: 0344-5704 [Print] Germany
PMID11592348 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antineoplastic Agents
  • Carbazoles
  • Enzyme Inhibitors
  • Glucosides
  • Indoles
  • Topoisomerase I Inhibitors
  • edotecarin
Topics
  • Adult
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Brain Neoplasms (drug therapy)
  • Carbazoles (therapeutic use)
  • Child
  • Enzyme Inhibitors (therapeutic use)
  • Female
  • Glioma (drug therapy)
  • Glucosides (therapeutic use)
  • Humans
  • Indoles
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Survival Rate
  • Topoisomerase I Inhibitors
  • Transplantation, Heterologous
  • Treatment Outcome
  • Tumor Cells, Cultured

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