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Cancer Chemother Pharmacol. 2003 Mar;51(3):231-9. Epub 2003 Feb 27.

Phase I trial of continuous infusion 5-aza-2'-deoxycytidine.

Author information

1
Department of Medicine, Keck/USC School of Medicine, Los Angeles, CA, USA.

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/m(2). Grade 4 neutropenia was found in two of five patients at 40 mg/m(2) and one of six patients at 30 mg/m(2). No objective responses were seen in this study. Steady-state DAC levels of 0.1 to 0.2 microM were achieved in the 30 and 40 mg/m(2) 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/m(2) per day for a 72-h intravenous infusion. Changes in gene methylation were observed.

PMID:
12655442
DOI:
10.1007/s00280-002-0563-y
[Indexed for MEDLINE]

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