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Topoisomerase I Inhibitors Promising as Therapy for CNS Tumors

Topoisomerase I Inhibitors Promising as Therapy for CNS Tumors

DURHAM, North Carolina—Topoisomerase-I inhibitors in combination with
carmustine (BiCNU, Gliadel) or temozolomide (Temodar) have produced promising
early results in patients with malignant gliomas, according to Henry S.
Friedman, MD. He is the James B. Powell, Jr., Professor of Neuro-Oncology at
Duke University Medical Center in Durham, North Carolina.

Studies of topotecan (Hycamtin), irinotecan (Camptosar), and
9-amino-camptothecin in subcutaneous xenografts of gliomas showed that these
agents could retard tumor growth in several cell lines, Dr. Friedman said.
Growth delays produced by irinotecan were greater than with other agents.
Similar effects were seen in xenografts of medulloblastomas and ependymomas.

Topoisomerase-I inhibitor treatment also produced tumor regressions in
subcutaneous xenograft models of gliomas, medulloblastomas, and other central
nervous system (CNS) tumors. Subsequent studies in intracranial xenograft
models showed that treatment with topoisomerase-I inhibitors could increase
median survival, Dr. Friedman said.

Irinotecan Studies

Based in part on these data, irinotecan was tested in a phase II trial in
malignant glioma. The trial enrolled 60 patients with recurrent malignant
glioma who had measurable disease and no more than one prior chemotherapy
regimen. Patients were treated with irinotecan at 125 mg/m² weekly for 4 weeks
followed by a 2-week rest. Physical examination and magnetic resonance imaging
(MRI) were done after every cycle.

"There were 9 partial responses, 4 minimal responses, and 13 patients
with disease stabilization," Dr. Friedman said. Disease progressed in 34
patients.

Toxicity was notably mild, primarily mild diarrhea, minimal neutropenia, and
minimal thrombocytopenia.

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