Abstract | PURPOSE: PATIENTS AND METHODS: Patients were treated every 28 days with TMZ at 150-200 mg/m2 once daily on days 1-5 and MT at 25 mg twice daily on days 8-28. Results were compared to our database of anaplastic glioma patients treated at recurrence. A subanalysis of the relationship between MT-induced joint-related toxicity and anticonvulsant status was carried out. RESULTS: Forty-nine patients were enrolled; all were assessable for toxicity, and 46 were included in the efficacy analysis. Joint and muscle complaints occurred in 32 patients (65%); 1 patient was removed from the study due to toxicity. The best protocol response was a complete response in 1 patient and a partial response in 2 patients (3/46=7%, 95% confidence interval (CI)=1, 18). Median time to progression was 24 weeks (95% CI=16, 56), and the progression-free survival (PFS) rate was 48% at 6 months (95% CI=35%, 65%), which surpassed the protocol objective of 40%. Sub-analysis showed a positive impact of joint-related toxicity due to MT on PFS whether or not patients were taking CYP450 enzyme-inducing anticonvulsants. CONCLUSIONS: Even though this regimen is more efficacious than our comparator of historical controls in recurrent AG, the regimen was roughly equivalent to single-agent TMZ and was associated with additional toxicity. The sub-analysis suggests pharmacokinetic and drug-drug interactions which may positively impact responses to MT.
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Authors | Morris D Groves, Vinay K Puduvalli, Charles A Conrad, Mark R Gilbert, W K Alfred Yung, Kurt Jaeckle, Vivien Liu, Kenneth R Hess, Kenneth D Aldape, Victor A Levin |
Journal | Journal of neuro-oncology
(J Neurooncol)
Vol. 80
Issue 1
Pg. 83-90
(Oct 2006)
ISSN: 0167-594X [Print] United States |
PMID | 16639492
(Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anticonvulsants
- Enzyme Inhibitors
- Hydroxamic Acids
- Dacarbazine
- Cytochrome P-450 Enzyme System
- marimastat
- Temozolomide
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Topics |
- Anticonvulsants
(administration & dosage)
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Brain Neoplasms
(drug therapy, mortality, pathology)
- Cytochrome P-450 Enzyme System
(drug effects)
- Dacarbazine
(administration & dosage, adverse effects, analogs & derivatives)
- Disease-Free Survival
- Enzyme Inhibitors
(therapeutic use)
- Glioma
(drug therapy, mortality, pathology)
- Humans
- Hydroxamic Acids
(administration & dosage, adverse effects)
- Joint Diseases
(chemically induced)
- Joints
(drug effects)
- Neoplasm Recurrence, Local
(drug therapy)
- Survival Analysis
- Temozolomide
- Treatment Outcome
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