Approximately 65-75% of patients with acute myelogenous leukemia who receive remission induction therapy will enter a complete remission. Without post-remission consolidation therapy, these patients would experience recurrence and ultimately die of their leukemia. Post-remission consolidation can be achieved following administration of a single course of high-dose chemotherapy supported with autologous or allogeneic stem cells or with multiple treatment courses of lower dose chemotherapy. Lower dose consolidation chemotherapy is the main treatment option for patients who are older, do not have an appropriate bone marrow or stem cell donor, or do not have access to a center or clinic where high-dose chemotherapy is offered as treatment. Several institutions associated with the Cancer and Leukemia Group B performed a clinical trial that evaluated 3 different doses of Cytosar-U® (cytarabine) as post-remission consolidation treatment in patients with acute myelogenous leukemia in complete remission. The results of this clinical trial were subsequently published in the New England Journal of Medicine.

In this clinical trial, 596 patients who achieved a complete remission following standard remission induction therapy for acute myelogenous leukemia were assigned to receive 1 of 3 post-remission consolidation chemotherapy treatments with Cytosar-U®. Cytosar-U® was scheduled to be administered at a dose of 100 mg/day or 400 mg/day for 5 consecutive days or 3 grams/m2 twice a day for 3 days. Patients were scheduled to receive this treatment every month for 4 months assuming their bone marrow function recovered following each treatment course. Following completion of the 4 cycles of Cytosar-U® consolidation, patients received an additional 4 courses of low-dose Cytosar-U® therapy.

The results of this trial unequivocally demonstrated that more is better or higher doses of chemotherapy cured more patients than lower doses of chemotherapy for patients with acute myelogenous leukemia under the age of 60. At 4 years from treatment, 44% of patients receiving the highest dose of Cytosar-U® were alive without evidence of disease recurrence compared to only 24-29% of patients receiving lower doses of chemotherapy consolidation. Side effects from high-dose Cytosar-U® were significant with the majority of patients requiring repeated hospital admissions because of concerns of infection, multiple red blood cell and platelet transfusions, and 12% of patients experienced significant central nervous system toxicities. Only 62% of patients under the age of 60 were able to receive all 4 treatments with high-dose Cytosar-U® and 5% of patients died from complications of therapy.

While chemotherapy consolidation with Cytosar-U® was able to cure 45% of patients less than age 60, patients over age 60 did not have as encouraging results. Only 16% of patients were alive without evidence of disease recurrence in all 3 treatment groups. Only 1 in 3 patients over the age of 60 was able to receive all 4 treatment cycles with high-dose Cytosar-U®. Older patients also experienced significantly more neurologic toxicity. While a small number of patients over the age of 60 can be cured, it is clear that new treatment strategies are needed for the management of acute myelogenous leukemia in the elderly.

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This clinical trial demonstrates that high-dose Cytosar-U® consolidation chemotherapy for patients with acute myelogenous leukemia in complete remission cured 44% of patients under the age of 60. This 44% cure rate is equal or slightly less than equal to the cure rate reported for high-dose chemotherapy and autologous or allogeneic stem cell transplantation. Only 1 in3 patients will have a suitable allogeneic stem cell donor, and therefore, 2 out of 3 patients diagnosed with acute myelogenous leukemia will have to choose between consolidation treatment with multiple cycles of chemotherapy or a single course of high-dose chemotherapy supported by autologous stem cell transplantation. (New England Journal of Medicine, Vol 331, No 14, pp 896-903, 1994)

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