DURHAM, North CarolinaTopoisomerase-I inhibitors in combination with carmustine(Drug information on carmustine) (BiCNU, Gliadel) or temozolomide(Drug information on 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(Drug information on topotecan) (Hycamtin), irinotecan(Drug information on 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.
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.