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

Abstract

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.

• Authors: Lara J Kunschner, Howard Fine, Kenneth Hess, Kurt Jaeckle, Athanassios P Kyritsis, W K Alfred Yung
• Journal: Cancer investigation (Cancer Invest) Vol. 20 Issue 7-8 Pg. 948-54 ( 2002) ISSN: 0735-7907 [Print] England
• PMID: 12449727 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Comparative Study, Evaluation Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Carbamates
• Pyrazines
• Pyridines
• canertinib dihydrochloride

Topics

• 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