Safety and Efficacy of Oral Azacitidine (CC-486) Administered in Extended Treatment Schedules to Patients with Lower-Risk Myelodysplastic Syndromes | Aplastic Anemia and MDS International Foundation

Safety and Efficacy of Oral Azacitidine (CC-486) Administered in Extended Treatment Schedules to Patients with Lower-Risk Myelodysplastic Syndromes

Original Publication Date: 
Tuesday, January 1, 2013

Note: This review is based upon a presentation at the 2012 American Society of Hematology (ASH) Annual Meeting, December 7-10 in Atlanta, Georgia.The full abstract may be reviewed on the ASH Annual Meeting Web site. Search by entering the title in the search box. The abstract number is referenced to access the full report.

Abstract #424

Guillermo Garcia-Manero, MD1, Steven D. Gore, MD2, Suman Kambhampati, MD3*, Bart L Scott, MD, MS4, Ayalew Tefferi, MD5, Christopher R Cogle, MD6, William Edenfield, MD7*, Joel Hetzer, PhD8*, Keshava Kumar, PhD8* and Barry S. Skikne, MD9

Treatment for myelodysplastic syndrome (MDS) often involves the use of hypomethylating agents that kills unhealthy cells in bone marrow. Vidaza® (azacitidine), a hypomethylating agent, is the current standard treatment for high-risk MDS. Azacitidine is typically injected under the skin (subcutaneously) or into a vein (intravenously) once a day for 7 days, and the cycle is repeated every 4 weeks.

Researchers are studying a new, oral version of azacitidine in a multicenter, phase 1 clinical trial. This trial is enrolling patients with lower-risk MDS who need regular red blood cell transfusions, have thrombocytopenia (low platelet count), or both. 

At the time this report was written, 53 patients had been treated with 1 to 12 oral azacitidine cycles. The 26 patients in Group 1 (average age 73 years) were treated with 300 mg oral azacitidine once a day for 14 days in repeated 28-day cycles. Group 2 (average age 70 years) was treated with the same dose every day for 21 days in repeated 28-day cycles.

Key Findings:

  • 39% of Group 1 and 30% of Group 2 responded to the treatment.
  • 47% of Group 1 and 33% of Group 2 did not need red blood cell transfusions for 56 days.
  • Six patients (three in each group) dropped out of the study because of side effects that might have been related to the treatment.
  • Response rates among the 33 patients treated with at least four cycles of oral azacitidine were 47% in Group 1 and 50% in Group 2.

Conclusions:

  • Oral azacitidine in 300 mg daily doses over 14 or 21 days of repeated 28-day cycles was effective and well tolerated in patients with lower-risk MDS in this study.
  • Outcomes were similar in patients treated over 14 or 21 days of repeated 28-day cycles.
  • The most common side effects were gastrointestinal and were manageable.
  • Oral azacitidine should be studied further in randomized clinical trials.
Reviewer Bio: