Details

Autor(en) / Beteiligte

• APARICIO, A
• EADS, C. A
• LEONG, L. A
• LAIRD, P. W
• NEWMAN, E. M
• SYNOLD, T. W
• BAKER, S. D
• ZHAO, M
• WEBER, J. S

Titel

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

Ist Teil von

• Cancer chemotherapy and pharmacology, 2003-03, Vol.51 (3), p.231-239

Ort / Verlag

Berlin: Springer

Erscheinungsjahr

2003

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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.