Lomustine and Intermediate Dose Cytarabine in Older Patients With AML

A multicenter randomized trial was performed comparing induction therapy (IC: Idarubicin and Cytarabine, 5+7) to ICL (the same drugs plus lomustine (CCNU), 200mg\m2 orally at day 1). Patients in complete remission (CR) were then randomized to receive either maintenance therapy or intensification with intermediate-dose cytarabine and idarubicin followed by maintenance therapy.

Induction therapy: Patients were randomized to receive idarubicin plus cytarabine (IC) or the same drugs plus lomustine (ICL), the latter given at the dose of 200 mg/m2 orally at day 1. Patients with persistent leukemia in the bone marrow, defined by at least 20% marrow cellularity with more than 5% blasts on day 14 or at a subsequent time point following initiation of induction therapy, received a second course of induction chemotherapy identical to the initial induction course. Non-responders to the second induction course were taken off the protocol.

Consolidation therapy: After completing induction treatment, patients who were in complete remission after 1 or 2 induction courses received a course of consolidation (IC’) therapy with idarubicin and subcutaneous cytarabine. Subsequently, if stable remission persisted, the patients received maintenance therapy or maintenance therapy preceded by a second consolidation (IIC) with intermediate-dose cytarabine. Randomization was performed as soon as CR was achieved.

Maintenance therapy: This was conducted in all patients with persisting CR one month after completing the first (IC) or second (IIC) consolidation and consisted of the following: five courses of combination chemotherapy at 1, 3, 6, 9 and 13 months from the last consolidation, namely cytarabine (subcutaneously) and idarubicin and between these courses for one year: a continuous regimen of methotrexate and 6-mercaptopurine, as alternating 10 day-courses .

Inclusion Criteria:

• Patients aged 60 years and older with de novo AML according to FAB criteria
• With normal cardiac function with left ventricular ejection fraction >= 50%, absence of unstable cardiac arrhythmia or unstable angina.
• Unimpaired renal (creatinin <180µmol\L)
• Unimpaired liver (bilirubin <35µmol\L) functions.
• Performance status <3
• Signed and dated informed consent.

Exclusion Criteria:

• Acute promyelocytic leukemia
• Patients with myeloproliferative syndromes prior to diagnosis of AML
• Patients who previously had myelodysplastic syndrome
• Patients pretreated with chemo- or radiotherapy
• Performance status <2
• Positive serology for HIV