CI-980 for the treatment of recurrent or progressive malignant gliomas: national central nervous system consortium phase I-II evaluation of CI-980
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Kunschner, L. J.
Fine, H.
Hess, K.
Jaeckle, K.
Kyritsis, A. P.
Yung, W. K.
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peer-reviewed
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Cancer Invest
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OBJECTIVE: The purpose of this phase I/II trial was to determine the maximal tolerated dose of CI-980, and determine efficacy against malignant glioma. BACKGROUND: The CI-980 is a synthetic mitosis inhibitor that acts via the colchicine binding site on tubulin. Broad in vitro activity has been seen in a variety of human and murine tumor models. Phase I studies have demonstrated schedule dependent toxicity of CI-980. Dose-limiting toxicity was neurologic when CI-980 was given as a 24-hr infusion and hematologic when given over 72 hr at higher doses. METHODS: Twenty-four patients ages 29-65 entered this study. Six patients were treated on the phase I arm at three escalating dose levels ranging from 10.5 to 13.5 mg/m2, given over 72 hr. Eighteen patients were then treated at the highest tolerated dose, 13.5 mg/m2 per cycle. Treatment response was based on serial MRI imaging characteristics. RESULTS: The phase II study was stopped at the end of the first stage due to poor treatment response. There were no partial or complete responses, (0/24) 95% CI = 0-14%. Four patients (4/24) had a best treatment response of stable disease/no change. Median time to progression for all patients was 6.4 weeks (95% CI: 6-9 weeks). Dose-limiting toxicity was grade 3-4 granulocytopenia. Three episodes of neurotoxicity manifested by a moderate cerebellar dysfunction were seen. CONCLUSIONS: These results fail to demonstrate the significant activity of CI-980 against recurrent glioma.
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Adult, Aged, Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use, Brain Neoplasms/*drug therapy, Carbamates/administration & dosage/adverse effects/*therapeutic use, Disease-Free Survival, Female, Glioma/*drug therapy, Humans, Infusions, Intravenous, Male, Maximum Tolerated Dose, Middle Aged, Neoplasm Recurrence, Local/*drug therapy, Pyrazines/administration & dosage/adverse effects/*therapeutic use, Pyridines/administration & dosage/adverse effects/*therapeutic use, Survival Rate, Thrombocytopenia/chemically induced, Treatment Outcome
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http://www.ncbi.nlm.nih.gov/pubmed/12449727
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en
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Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής