Etoposide in acute leukemia. Past experience and future perspectives

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Etoposide monotherapy shows activity in relapsed/refractory acute myeloid leukemia (AML), achieving 10-25% complete response (CR) rates.
• Etoposide has been safely combined with cytarabine, azacytidine, vinca alkaloids, and anthracyclines, yielding 20-60% remission rates in previously treated AML.
• Limited data suggest etoposide's activity in acute lymphoblastic leukemia (ALL), particularly with cytarabine or aclacinomycin.

Purpose of the Study:

• To evaluate the efficacy of the NOVE combination (mitoxantrone plus etoposide) in patients with refractory AML.
• To investigate the impact of etoposide administration duration on CR rates within the NOVE regimen.
• To assess a sequential IDAC (idarubicin/cytarabine) and NOVE regimen for the primary treatment of adult AML.

Main Methods:

• A Phase I/II trial administered mitoxantrone (10 mg/m²/d, days 1-5) plus etoposide (100 mg/m²/d for 3, 4, or 5 days) to patients with refractory AML.
• A pilot study employed a sequential regimen of IDAC or NOVE, with cycles determined by patient response, for primary AML treatment.

Main Results:

• The NOVE combination achieved a 43% CR rate in 61 patients with refractory AML.
• Extended etoposide duration in the NOVE regimen was associated with higher CR rates.
• The sequential IDAC/NOVE strategy resulted in 18 of 20 patients achieving CR in a pilot study.

Conclusions:

• The NOVE combination, particularly with extended etoposide administration, is an effective treatment for refractory AML.
• A sequential IDAC/NOVE regimen shows promising results for the primary treatment of adult AML.
• Further studies are warranted to confirm the efficacy of the sequential IDAC/NOVE strategy.