Effectiveness of Various Dosage Regimens of Azacitidine In Patients with Myelodysplastic Syndromes: Safety and Efficacy Final Data From the Spanish Azacitidine Compassionate Use Registry

Azacitidine (AZA), an hypomethylating agent approved in Europe for the treatment of MDS, prolongs the median survival time of patients included in clinical trials (Fenaux et al., 2009). AZA was available for clinical trials or compassionate use in Spain before receiving marketing authorization in Spain in May 2009. The dosage regimen of AZA in routine clinical practice (not in clinical trials) may have been adapted to the care environment at each center. We hereby present the results of the final analysis from a longitudinal, multicenter Spanish patient registry.

This analysis retrospectively gathers clinical data about the treatment and disease progression of patients with MDS who had received AZA in compassionate use conditions, and for whom the dosage regimen was documented. AZA doses were administered to patients in three different dosage regimens at the beginning of each 28-day cycle; group A: days 1–5 (M-F)/group B: days 1–5, 8–9 (M-F, M-Tu)/group C: days 1–7 (M-Su). Patients who received an initial dose other than 75mg/m² were excluded from this analysis. Treatment assignment was based on the patient's condition and on the viability of the care environment for drug administration during weekends. Treatment effectiveness and tolerance were analyzed based on the patients’ basal conditions, stratified by the dosage schedule.

Data were collected from 181 patients with MDS according to the WHO diagnostic criteria. Their demographic characteristics were similar at the beginning of the study, except for their ECOG performance status, with a statistically-significant higher prevalence of an ECOG ≥ 2 in the administration group C (table 1). The three dosage regimens of AZA were applied in the following proportions: group A 32.3%, group B 27.5% and group C 36.5%. The median number of administered cycles was similar for all groups (6 cycles). The overall response rates for the treatment (IWG 2006 criteria) were as follows: group A 38%, group B 71% and group C 52% (p group A vs. B=0.0005, p group A vs. C=0.0982, p group B vs. C =0.0418). No differences were observed in survival between chromosome 7 abnormalities and an intermediate abnormal karyotype (HR 1.11; p=0.83). AZA treatment was well tolerated. Most of the adverse events were hematological. The adverse event profile varied based on the dose regimen group (Table).

The data of the 181 patients evaluated shows that in routine clinical practice effectiveness and tolerance differ when different dosage regimens are used. A better effectiveness/tolerance profile is observed in those regimens with a lower period of time to next cycle.

García:Celgene : Research Funding.