or inducers has not been studied.
The potential of azacitidine to inhibit cytochrome P450 (CYP) enzymes is not known.
In vitro studies with human cultured hepatocytes indicate that azacitidine at concentrations of 1.0 μM to 100 μM does not induce CYP 1A2, 2C19, or 3A4/5.
CLINICAL STUDIES
A randomized, open-label, controlled trial carried out in 53 U.S. sites compared the safety and efficacy of subcutaneous Vidaza plus supportive care with supportive care alone (“observation”) in patients with any of the five FAB subtypes of myelodysplastic syndromes (MDS): refractory anemia (RA), RA with ringed sideroblasts (RARS), RA with excess blasts (RAEB), RAEB in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL). RA and RARS patients were included if they met one or more of the following criteria: required packed RBC transfusions; had platelet counts ≤ 50.0 x 109/L; required platelet transfusions; or were neutropenic (ANC < 1.0 x 109/L) with infections requiring treatment with antibiotics. Patients with acute myelogenous leukemia (AML) were not intended to be included. Baseline patient and disease characteristics are summarized in Table 1; the 2 groups were similar.
Vidaza was administered at a subcutaneous dose of 75 mg/m2 daily for seven days every four weeks. The dose was increased to 100 mg/m2 if no beneficial effect was seen after two treatment cycles. The dose was decreased and/or delayed based on hematologic response or evidence of renal toxicity. Patients in the observation arm were allowed by protocol to cross over to Vidaza if they had increases in bone marrow blasts, decreases in hemoglobin, increases in red cell transfusion requirements, or decreases in platelets, or if they required a platelet transfusion or developed a clinical infection requiring treatment with antibiotics. For purposes of assessing efficacy, the primary endpoint was response rate (as defined in Table 2).
Of the 191 patients included in the study, independent review (adjudicated diagnosis) found that 19 had the diagnosis of AML at baseline. These patients were excluded from the primary analysis of response rate, although they were included in an intent-to-treat (ITT) analysis of all patients randomized. Approximately 55% of the patients randomized to observation crossed over to receive Vidaza treatment.
Table 1. Baseline Demographics and Disease Characteristics
|
|
Vidaza
(N=99) |
Observation
(N=92) |
|
Gender (n%) |
|
|
|
Male |
72 (72.7) |
60 (65.2) |
|
Female |
27 (27.3) |
32 (34.8) |
|
Race (n%) |
|
|
|
White |
93 (93.9) |
85 (92.4) |
|
Black |
1 (1.0) |
1 (1.1) |
|
Hispanic |
3 (3.0) |
5 (5.4) |
|
Asian/Oriental |
2 (2.0) |
1 (1.1) |
|
Age (years) |
|
|
|
N |
99 |
91 |
|
Mean ± SD |
67.3 ± 10.39 |
68.0 ± 10.23 |
|
Range |
31 - 92 |
35 - 88 |
|
Adjudicated MDS diagnosis at study entry (n%) |
|
