The potential of topoisomerase I inhibitors in the treatment of CNS malignancies: Report of a synergistic effect between topotecan and radiation

John P. Lamond, Minesh P. Mehta, David A. Boothman

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Despite innovations in imaging, surgery, and radiation therapy, local failure remains the principle clinical problem in most CNS malignancies. To date, chemotherapy has not made a major impact in the treatment of most adult CNS tumors. The inroads made by chemotherapy in pediatric CNS malignancies suggest that novel drugs, or drug combinations, may improve therapy. Topoisomerase I (Topo I) inhibitors are a relatively new group of chemotherapy drugs with a novel mechanism of action. Drugs in this group currently undergoing clinical trials are the Camptothecin analogues Topotecan, CPT-11, and 9-aminocamptothecin. There is substantial preclinical and some clinical evidence to suggest that these drugs could be useful in the treatment of CNS malignancies. Preclinical studies with the water soluble Topo I inhibitor, Topotecan, demonstrate antineoplastic activity in a variety of CNS malignancies. In addition, Topotecan has good CNS penetration in primates, and recent preliminary phase I and II clinical trials of Topotecan in pediatric and adult CNS malignancies have been promising. In this paper, we describe the unique mechanism of action, antineoplastic activity, and radiosensitizing properties of Topo I inhibitors. We present the first report demonstrating potentiation of radiation lethality by Topotecan in a human glioma (D54) cell line. The dose enhancement ratio was 3.2 at 10% survival. Thus, there is evidence to suggest that Topo I inhibitors may be beneficial in the treatment of CNS neoplasms on the basis of their antineoplastic activity alone, as well as their radiosensitizing effects. Two clinical trials which utilize concurrent Topotecan and radiation in the treatment of pediatric and adult CNS malignancies are discussed.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalJournal of Neuro-Oncology
Volume30
Issue number1
StatePublished - 1996

Fingerprint

Topoisomerase I Inhibitors
Topotecan
Radiation
Neoplasms
Antineoplastic Agents
irinotecan
9-aminocamptothecin
Therapeutics
Pediatrics
Drug Therapy
Pharmaceutical Preparations
Clinical Trials
Radiation-Sensitizing Agents
Camptothecin
Phase II Clinical Trials
Clinical Trials, Phase I
Drug Combinations
Glioma
Primates
Radiotherapy

Keywords

  • Glioma
  • Radiosensitizers
  • Topoisomerase I
  • Topotecan

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

Cite this

The potential of topoisomerase I inhibitors in the treatment of CNS malignancies : Report of a synergistic effect between topotecan and radiation. / Lamond, John P.; Mehta, Minesh P.; Boothman, David A.

In: Journal of Neuro-Oncology, Vol. 30, No. 1, 1996, p. 1-6.

Research output: Contribution to journalArticle

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