A phase 2 study of vorinostat in acute myeloid leukemia.

Abstract

BACKGROUND:

This two-stage, multi-institutional, randomized phase 2 trial assessed the toxicity and response rate associated with two treatment schedules of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamic acid; SAHA) in patients with relapsed acute myeloid leukemia and in selected untreated patients with high-risk acute myeloid leukemia.

DESIGN AND METHODS:

Patients with relapsed or untreated acute myeloid leukemia who were not candidates for chemotherapy entered one of the two treatment arms. In both arms a total dose of 8400 mg of vorinostat was delivered in each 21-day cycle of treatment: in arm A the dose regimen was 400 mg daily whereas in arm B the dose regimen was 200 mg three times daily for 14 days followed by 1 week rest.

RESULTS:

Data from all 37 patients were used for the analyses. In arm A (n=15), the confirmed complete remission rate was 0% (95% CI, 0% to 23%); this arm was closed at the planned interim analysis. In arm B (n=22), the confirmed complete remission rate was 4.5% (1 response; 95% CI, 0.4% to 24%), with a duration of response exceeding 398 days. The median time to treatment failure in arm A was 42 days (95% CI, 26 to 57); although a minimum of four cycles of treatment were planned, 11 patients (79%) received no more than two cycles. The median time to treatment failure in arm B was 46 days (95% CI, 20 to 71); 13 patients (59%) received no more than two cycles of treatment.

CONCLUSIONS:

Vorinostat monotherapy demonstrated minimal activity in this group of patients with acute myeloid leukemia. Therapy was discontinued in many patients before the planned four cycles had been administered, either because of failure of vorinostat to control the leukocyte count or patients' and physicians' preference. Future studies of vorinostat in acute myeloid leukemia should focus on combinations with other drugs with which it might interact pharmacodynamically. ClinicalTrials.gov Identifier: NCT00305773.

• Authors: Eric W Schaefer, Arturo Loaiza-Bonilla, Mark Juckett, John F DiPersio, Vivek Roy, James Slack, Wenting Wu, Kristina Laumann, Igor Espinoza-Delgado, Steven D Gore, Mayo P2C Phase II Consortium
• Journal: Haematologica (Haematologica) Vol. 94 Issue 10 Pg. 1375-82 (Oct 2009) ISSN: 1592-8721 [Electronic] Italy
• PMID: 19794082 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxamic Acids
• Vorinostat

Topics

• Adult
• Aged
• Aged, 80 and over
• Female
• Humans
• Hydroxamic Acids (therapeutic use)
• Leukemia, Myeloid, Acute (blood, drug therapy, pathology)
• Male
• Middle Aged
• Vorinostat