CI-980 for the treatment of recurrent or progressive malignant gliomas: national central nervous system consortium phase I-II evaluation of CI-980 (Journal article)

Kunschner, L. J./ Fine, H./ Hess, K./ Jaeckle, K./ Kyritsis, A. P./ Yung, W. K.

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.
Institution and School/Department of submitter: Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής
Keywords: 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
ISSN: 0735-7907
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά)

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