Pilot phase I-II study on 5-aza-2'-deoxycytidine (Decitabine) in patients with metastatic lung cancer

Anticancer Drugs. 1997 Apr;8(4):358-68. doi: 10.1097/00001813-199704000-00008.


5-Aza-2'-deoxycytidine (5-AZA-CdR, Decitabine) is a nucleoside analog and an active drug for the therapy of acute leukemia. The incorporation of 5-AZA-CdR into DNA blocks DNA methylation and can result in the activation of specific genes, such as tumor suppressor genes. This novel mechanism of action of 5-AZA-CdR stimulated our interest in its potential for cancer therapy in patients with lung cancer. Using a colony assay we observed that 5-AZA-CdR showed a potent antineoplastic effect against two human lung carcinoma cell lines. The objective of this preliminary phase I-II study was to evaluate the toxicity and clinical efficacy of 5-AZA-CdR in patients with stage IV non-small cell lung carcinoma. There were 15 patients that entered the clinical study. For nine assessable patients that received 5-AZA-CdR by a single 8 h i.v. infusion of 200-660 mg/m2 for one or more cycles, the median survival duration was 6.7 months, with three patients surviving more than 15 months. The steady-state plasma concentration of 5-AZA-CdR during the infusion was estimated in some patients and was in the same range that produced activation of a tumor suppressor gene in human lung tumor cell lines as reported by other investigators. The major side effect of 5-AZA-CdR was hematopoietic toxicity which required a 5-6 week recovery period before the next cycle of therapy. This study suggests that 5-AZA-CdR may have some clinical activity against metastatic lung carcinoma using this type of dose schedule.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / blood
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Azacitidine / adverse effects
  • Azacitidine / analogs & derivatives*
  • Azacitidine / blood
  • Azacitidine / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Squamous Cell / drug therapy
  • Decitabine
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pilot Projects
  • Tumor Cells, Cultured / drug effects


  • Antimetabolites, Antineoplastic
  • Decitabine
  • Azacitidine