a randomized study of post-remission therapy in elderly patients with acute myelogenous leukemia.

Conditions: Acute Myeloid Leukemia

Summary: in this alfa-9803 trial in aml patients aged 65 years or more, we randomly compared idarubicin or daunorubicin throughout the study (first randomization) and two different post-remission strategies (second randomization): one single intensive consolidation course similar to induction versus six ambulatory cycles with one dose of idarubicin/daunorubicin (day 1) and 2x60 mg/m2/d cytarabine sc (day 1 to 5) delivered in out-patients on a monthly basis. primary endpoint was 2-year overall survival (os). study hypotheses were equivalence for the idarubicin/daunorubicin comparison and a 15% difference in 2-year os for the post-remission therapy comparison.

patients were randomized at baseline (first r1 randomization) to receive either daunorubicin (dnr) or idarubicin (ida) as an anthracycline for induction and post-remission therapy. this first randomization was stratified on centers and aml type (de novo versus post-mds aml). induction chemotherapy consisted of a 4+7 course with either dnr at a daily dosage of 45 mg/m2 or ida at a daily dosage of 9 mg/m2 for four days (day 1 to day 4) in combination with 200 mg/m2 cytarabine per day as a continuous iv infusion for seven days (day 1 to 7). lenograstim granulocyte colony-stimulating factor (g-csf) was administered in all patients from day 9 until myeloid recovery (3 consecutive days with pmn more than 1.0 g/l) by iv infusion and at a daily dosage of 263 microg/day for a maximum of 28 days. a blood and marrow aspiration smear examination was performed at day 21. a salvage course of chemotherapy may be offered to patients with persistent leukemia (defined below), but only if they did not present acquired contra-indication to further intensive chemotherapy (baseline criteria). salvage consisted of six 1-hour iv bolus of intermediate-dose cytarabine (500 mg/m2/12h day 1 to 3) combined to mitoxantrone (mtz) at a daily dosage of 12 mg/m2 for two days (day 3 and 4). g-csf administration was stopped before salvage onset and restarted from day 5 of the salvage course until myeloid recovery for a maximum of 28 days. patients reaching complete remission (cr) after induction or induction followed by salvage were eligible for a second r2 randomization between mild versus intensive post-remission therapy, but only if they did not present acquired contra-indication to further intensive chemotherapy (baseline criteria). this second randomization was stratified on centers, aml groups (de novo versus post-mds aml), and first randomization groups. mild post-remission therapy was administered in out-patients and consisted of six 1+5 monthly courses with either 45 mg/m2 dnr or 9 mg/m2 ida for one day (day 1) in combination with 60 mg/m2/12h cytarabine as a sc infusion for five days (day 1 to 5). no g-csf support was given after these six courses. intensive post-remission therapy required another hospitalization and was a repetition of the first 4+7 induction administered at the same doses and followed by g-csf administration as well.

Eligibility criteria:
inclusion criteria: male or female aged 65 years or more. patient with previously untreated aml except m3 in the fab classification. patient with previously untreated transformed refractory anemia with excess blasts (raeb-t). patients with aml secondary to a previously untreated myelodysplastic syndrome (mds), documented or not, are eligible, as well as those with raeb-t evolving from a previous known mds. patients with a performance status \< 3. patient who has given his/her written informed consent. exclusion criteria: patients with aml3 in the fab classification. patients with blast crisis of previously known myeloproliferative syndrome. patients with aml secondary to previous treatment with cytotoxic chemotherapy or radiotherapy (therapy-related aml). patients with another concommitant neoplasia. patients with leukemic central nervous system involvement. patients with a grade \> 2 uncontrolled infection. patients with grade \> 2 visceral contra-indications to treatment with induction chemotherapy (except if leukemia-related). bilirubin \> 2 times the normal range of the laboratory. serum creatinine \> 2 times the normal range of the laboratory. patients with cardiac contra-indication to treatment with anthracyclines.

Keywords: acute myeloid leukemia older patients patient aged 65 years or more