A phase i study of 5-azacytidine and erlotinib in advanced solid tumor malignancies

Julie Bauman, Claire Verschraegen, Steven Belinsky, Carolyn Muller, Teresa Rutledge, M. Fekrazad, Meera Ravindranathan, Sang Joon Lee, Dennie Jones

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Introduction: The epidermal growth factor receptor (EGFR) is a validated target in malignancy; however, patients with wild type EGFR obtain little sustained benefit from anti-EGFR monotherapy. Epigenetic therapy to reactivate tumor suppressor genes may enhance the anti-proliferative effect of erlotinib. This phase I study evaluated the combination of erlotinib and 5-azacytidine for safety and maximal tolerated dose (MTD). Methods: Thirty patients with advanced solid tumors were treated in a standard 3 + 3 cohort design. Erlotinib was dosed at 150 mg daily, and 5-azacytidine was escalated by increasing the number of daily doses of 75 mg/m 2 per cycle. Patients were followed for dose-limiting toxicity (DLT). Efficacy was assessed by RECIST criteria. Results: Common non-hematologic toxicities included rash, diarrhea, nausea, and fatigue; the majority was ≥ Grade 2. DLTs included conjunctivitis in cohort 1 and infusion reaction in cohort 2. No DLTs occurred in cohorts 3, 4, or 5; however, 2 serious neutropenic infections arose in cohort 5 after cycle 1. Cohort 4 was expanded to 6 patients and was the MTD. Partial response (lung, ovarian) and stable disease occurred in 2 and 11 patients, respectively. Median progression-free survival was 2 months. Two patients with lung and larynx cancer had prolonged stable disease. Conclusion: The combination of erlotinib and 5-azacytidine was well tolerated with interesting clinical activity in lung, head and neck, and ovarian cancer. The recommended dose for phase II study is erlotinib 150 mg daily and 5-azacytidine 75 mg/m 2 daily on days 1-4 and 15-18 of a 28-day cycle.

Original languageEnglish (US)
Pages (from-to)547-554
Number of pages8
JournalCancer Chemotherapy And Pharmacology
Issue number2
StatePublished - Feb 2012
Externally publishedYes


  • 5-azacytidine
  • Clinical trial
  • DNA methylation
  • Epidermal growth factor receptor
  • Epigenetic
  • Erlotinib
  • Phase I

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)


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