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

Cancer Chemother Pharmacol. 2003 Mar;51(3):231-9. doi: 10.1007/s00280-002-0563-y. Epub 2003 Feb 27.


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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects*
  • Antimetabolites, Antineoplastic / pharmacology
  • Azacitidine / administration & dosage
  • Azacitidine / adverse effects*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Biopsy
  • DNA Methylation / drug effects*
  • DNA, Neoplasm
  • Decitabine
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Polymerase Chain Reaction


  • Antimetabolites, Antineoplastic
  • DNA, Neoplasm
  • Decitabine
  • Azacitidine