Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 26, No 15S (May 20 Supplement), 2008: 7097
© 2008 American Society of Clinical Oncology

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Abstract

A phase II study of intravenous azacitidine alone in patients with myelodysplastic syndromes: NCT0038495

Washington University St. Louis, St. Louis, MO

7097

Background: 5-Azacytidine (Aza) has been shown to provide a survival benefit in the treatment of myelodysplastic syndromes (MDS). While Aza was first approved for subcutaneous (SC) administration, SC injection site reactions are not uncommon, especially in thrombocytopenic patients. Aza is FDA approved for short intravenous (IV) infusion for 7 days and is anticipated to be efficacious from pharmacokinetic profiling, but prospective efficacy data for this route are lacking. In addition, the 7 day treatment course presents logistic problems in an outpatient setting. Methods: To determine the efficacy of short IV infusion Aza, an open-label, single-arm, single-center phase II study of IV Aza in MDS, defined by FAB classification was undertaken. Subjects previously treated with Aza or decitabine were ineligible. Treatment consisted of Aza 75 mg/m² given as a 20 minute IV infusion once daily on Days 1–5 of a 28-day cycle. Response was evaluated by modified IWG 2006 criteria. Patients failing to achieve a CR after 2 cycles were eligible for an increased dose of 100 mg/m². Patients must have demonstrated at least a hematologic improvement to continue on study beyond 6 cycles. Study endpoints include determination of complete response (CR) and partial response (PR) rates. Results: Accrual began 8/17/06 with a target of 21 subjects. Eighteen subjects (median age 71.4 yr, range 53–82) have completed 1 cycle (median 3, range 1–9). Subjects consist of 4 RA, 10 RAEB, 2 RAEB-t, and 2 CMML, and IPSS risk of 1 Low, 5 Int-1, 10 Int-2, and 2 High. One subject achieved a CR and 2 have achieved a PR. Another 2 achieved an erythroid response, and 1 had stable disease. Nine subjects remain on study, 5 withdrew due to progressive disease, and 4 deaths have occurred on study (2 sepsis, 1 pneumonia, 1 MI). No deaths were attributed to Aza. Common adverse events (grades 1–4) include nausea (44%), emesis (39%), fatigue (44%), and hematologic toxicities (44%). Hematologic toxicities have resulted in transient treatment delays ( 4 weeks) and dose reductions but have not prevented subsequent treatment on study. Conclusions: This prospective study of IV AZA is approaching target accrual. Preliminary results demonstrate that IV AZA when administered over a 5 day period is safe and effective in patients with MDS.

Author Disclosure

Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genzyme AnorMED, Bayer, Celgene, Genzyme, MGI Pharma, Novartis, Pfizer, Pharmion Pharmion

Abstract presentation from the 2008 ASCO Annual Meeting