Abstract
Purpose: To identify a dose of the demethylating agent 5-aza-2′-deoxycytidine (DAC) with acceptable side effects, and to study its effect on the methylation patterns of relevant genes in tumor biopsies before and after treatment with a novel methylation assay using real-time PCR. Methods: A group of 19 patients with metastatic solid tumors were treated with DAC by continuous intravenous infusion over 72 h, days 1-3 of a 28-day cycle. Tumor biopsies were taken before and 7 days after starting DAC. Results: The dose levels studied were 20, 30 and 40 mg/m2. Grade 4 neutropenia was found in two of five patients at 40 mg/m2 and one of six patients at 30 mg/m2. No objective responses were seen in this study. Steady-state DAC levels of 0.1 to 0.2 μM were achieved in the 30 and 40 mg/m2 cohorts. Changes in methylation were observed, but no single gene consistently demonstrated evidence of demethylation. Conclusions: DAC was tolerated at a dose of 30 mg/m2 per day for a 72-h intravenous infusion. Changes in gene methylation were observed.
Original language | English (US) |
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Pages (from-to) | 231-239 |
Number of pages | 9 |
Journal | Cancer chemotherapy and pharmacology |
Volume | 51 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1 2003 |
Externally published | Yes |
Keywords
- Biopsy
- CpG
- Demethylation
- Gene expression
- Phase I
ASJC Scopus subject areas
- Oncology
- Toxicology
- Pharmacology
- Cancer Research
- Pharmacology (medical)