Fetal hemoglobin gene activation in a Phase II study of 5,6-dihydro-5-azacytidine for bronchogenic carcinoma

B. I. Carr, S. Rahbar, J. H. Doroshow, D. Blayney, D. Goldberg, L. Leong, Y. Asmeron

Research output: Contribution to journalArticlepeer-review

Abstract

5-Azacytidine and several of its analogues are known to inhibit DNA methylation, alter gene expression, and inhibit cell growth. We report a Phase II study in which we investigated the antineoplastic activity of 5,6-dihydro-5-azacytidine and its induction of fetal hemoglobin synthesis when given by a 5-day continuous i.v. infusion of 1650 mg/m2/day that was repeated every 21 days. Fetal hemoglobin was measured in all patients; increased synthesis was found in 13 of the 17, in the absence of clinically significant anemia. Of the four patients who did not develop increased fetal hemoglobin, three had only one cycle of therapy. Fourteen patients with bronchogenic carcinoma were treated, and ten were evaluable for disease response. Five patients had disease stability of 2 or more mo, and five progressed on treatment. Three additional patients with mesothelioma were treated, and the two who were evaluable for disease response had stabilization of their disease. Fifteen of the 17 patients who received 5,6-dihydro-5-azacytidine developed a pleuritic-type chest pain, 12 had abnormal electrocardiograms, and four developed positive antinuclear antibodies. No significant hemopoietic, hepatic, or renal toxicities were observed. This study demonstrates that 5,6-dihydro-5-azacytidine in the dose and schedule used has no significant therapeutic activity in the treatment of lung cancer but does possess an unusual spectrum of clinical toxicities as well as the property of inducing fetal hemoglobin synthesis.

Original languageEnglish
Pages (from-to)4199-4201
Number of pages3
JournalCancer Research
Volume47
Issue number15
Publication statusPublished - 1987

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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