Abstract 2663: Phase I study of azacitidine and cisplatin in patients with advanced head and neck or non-small cell lung cancer

Abstract

Abstract Background: DNA hypomethylation agents such as azacitidine may be used for epigenetic sensitization of cisplatin treatment, and therefore leading to improvement of treatment outcome. We conducted a phase I study of azacitidine and cisplatin to determine safety, toxicity, and effect of global DNA methylation in peripheral blood mononuclear cells. Methods: Azacitidine was given as subcutaneous injection daily from day 1 to day 5, and cisplatin was given at 75 mg/m2 IV on day 8. The treatment was repeated every 28 days. Four patients received azacitidine 37 mg/m2 daily from day 1 to day 5 on dose level 1. Two patients were treated on dose level 2, and received azacitidine 60 mg/m2 daily from day 1 to day 5. Peripheral blood samples were collected before and after azacitidine treatment. DNA was extracted from peripheral blood mononuclear cells, and subjected to gas chromatography/mass spectrometry to measure the level of global DNA methylation, as reflected by the ratio of 5-methylcytosine to the sum of 5-methylcytosine and cytosine. Results: No patient had dose-limiting toxicities. Four patients completed at least 2 cycles of treatment, and were evaluated for clinical response by CT scan and DNA methylation effect. One partial response was noted in patient with metastatic tongue cancer after 2 cycles of treatment on dose level 1 of azacitidine. This patient received total 3 cycles of treatment and achieved free of progression for about 15 months on chemotherapy holiday. One patient with recurrent salivary gland cancer achieved stable disease after 2 cycles of treatment on dose level 2, and maintained in free of progression for more than 6 months after 4 cycles of treatment. There was inhibition of global DNA methylation after azacitidine treatment ranging from 12 to 36% in all 4 patients. Furthermore, the inhibition of global DNA methylation was associated with the increase of fetal hemoglobin in patients’ peripheral blood. Conclusion: Sequential administration of azacitidine followed by cisplatin is well tolerated, and demonstrates encouraging activity in patients with advanced head and neck cancer. This combination deserves further clinical investigation to study the correlation between clinical response and biological effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2663. doi:1538-7445.AM2012-2663