Preliminary Results of a Phase II Study of Decitabine Administered Daily for 5 Days Every 4 Weeks to Adults with Myelodysplastic Syndrome (MDS).

Abstract Decitabine (Dacogen®), a hypomethylating agent, is FDA-approved for treatment of patients (pts) with all FAB subtypes of MDS. The approved regimen of 15 mg/m2 intravenously (IV) over 3 hours (hrs) every (q) 8 hrs for 3 days repeating q 6 wks demonstrated an overall improvement rate (CR+PR+HI) of 30% in MDS pts. An alternative regimen, in which decitabine is administered 20 mg/m2 IV over 1 hr once daily for 5 consecutive days repeating q 4 wks not only permits outpatient therapy, but also showed promising efficacy in a pilot study (Blood2007:109:52). This alternate regimen was evaluated in a multicenter study and preliminary results from this open-label single-arm Phase 2 study are reported. Eligible pts were ≥18 years (yrs) of age with MDS (de novo or secondary) of any FAB subtype (including chronic myelomonocytic leukemia with white count <12,000/μL) and International Prognostic Scoring System (IPSS) score ≥ 0.5 (Intermediate-1 (Int-1), Intermediate-2 (Int-2) and High-risk groups) as determined by complete blood counts, bone marrow assessment, and cytogenetics within 28 days of enrollment. Responses, the primary endpoint of the study, were assessed using International Working Group (IWG) criteria (Blood2000;96:3671), which existed at study initiation and also used in the Phase 3 trial with the FDA-approved 3-day regimen. Secondary objectives included evaluation of hematologic improvement, cytogenetic response, overall survival, time to acute myeloid leukemia progression or death, transfusion requirements, and toxicity. Ninety-nine pts enrolled: median age 72 yrs, 72% male, 89% de novo MDS, median time from diagnosis 153 days, and 29% with prior therapy for MDS. The distribution of IPSS risk groups was as follows: Low, 1%; Int-1, 53%; Int-2, 23%; and High, 23%. Pts have thus far been followed for one year after enrollment of the last pt, and the preliminary data are reported here. Investigator assessments of response, using pathology results at the individual study sites along with laboratory findings, demonstrated an overall improvement rate of 43%; central confirmation of results is ongoing. Pts received a median of 5 cycles of decitabine (range 1–17). Median survival has not been reached; a total of 62 pts continue to be followed. The most frequent adverse events were fatigue, fever, constipation, nausea, and neutropenia. Decitabine administered daily for 5 days in the outpatient setting demonstrated clinical activity with manageable toxicity profile in Int-1 to High risk MDS, suggesting that both the 3- and 5-day regimens provide meaningful clinical benefit to patients.

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