Decitabine for Treatment of Myelodysplastic Syndromes in Chinese Patients: An Open-Label, Phase-3b Study

Adv Ther. 2015 Nov;32(11):1140-59. doi: 10.1007/s12325-015-0263-8. Epub 2015 Nov 14.

Abstract

Introduction: The objective of this study was to evaluate the efficacy and safety of decitabine in Chinese patients with myelodysplastic syndrome (MDS).

Methods: Patients (≥18 years) who had a de novo or secondary MDS diagnosis according to French-American-British classification and an International Prognostic Scoring System score ≥0.5 were enrolled and randomized (1:1) to one of two decitabine regimens: 3-day treatment (3-h intravenous infusion of 15 mg/m(2) given every 8 h for three consecutive days/cycle/6 weeks) or 5-day treatment (1-h intravenous infusion of 20 mg/m(2) once daily on days 1-5/cycle/4 weeks). After a minimum of 30 patients were assigned to 3-day schedule, the remaining were assigned to the 5-day schedule. The primary efficacy endpoint was the overall response rate (ORR). Secondary outcome measures included hematologic improvement (HI), cytogenetic response rate, the time to acute myeloid leukemia (AML) progression, and overall survival (OS).

Results: In total, 132 of 135 enrolled patients (3-day treatment, n = 36; 5-day treatment, n = 99) discontinued treatment (major reasons included patient withdrawal/lack of efficacy, n = 48; adverse events, n = 23; and disease progression, n = 22). During the study, 35 of 132 (26.5%) patients from the intent-to-treat (ITT) group achieved significant (P < 0.001) ORR [3-day group (n = 10, 29.4%), P = 0.003; 5-day group (n = 25, 25.5%), P < 0.001]. The HI rate was similar between the 3-day (47.1%) and 5-day groups (48.0%). Cytogenetic response was achieved in 20 of the 30 (66.7%) patients who had a baseline cytogenetic abnormality. Fifty-three (40.2%) AML transformations or deaths occurred and the median AML-free survival time was 23.8 months for all patients from the ITT set; 24-month OS rate was 48.9%. Adverse events of myelosuppression-related disorders (85.6%) and infections (43.2%) were commonly reported.

Conclusion: Decitabine treatment was efficacious in Chinese patients with MDS with its safety profile comparable to the global studies of decitabine conducted to date.

Funding: Xian-Janssen Pharmaceutical Ltd. China (a company of Johnson & Johnson).

Trial registration: ClinicalTrials.gov identifier, NCT01751867.

Keywords: Chinese population; Decitabine; Hematology; Myelodysplastic syndrome (MDS); Oncology; Phase 3b.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Asian People
  • Azacitidine / administration & dosage
  • Azacitidine / adverse effects
  • Azacitidine / analogs & derivatives*
  • Azacitidine / therapeutic use
  • China
  • Decitabine
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Research Design
  • Survival Rate
  • Treatment Outcome
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • Decitabine
  • Azacitidine

Associated data

  • ClinicalTrials.gov/NCT01751867