Imatinib combined with mitoxantrone/etoposide and cytarabine is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis.

Abstract

BACKGROUND:

Despite advances in drug therapy and allogeneic stem cell transplantation (allo-SCT), the prognosis of patients with chronic myeloid leukemia (CML) in blast crisis remains poor. Imatinib has demonstrated synergistic effects in vitro with mitoxantrone, etoposide, and cytarabine.

METHODS:

A Phase I/II trial was performed in patients with CML myeloid blast crisis. Patients were treated with imatinib + mitoxantrone/etoposide in four cohorts: mitoxantrone 10 mg/m(2)/day and etoposide 100 mg/m(2)/day for 2 or 3 consecutive days and imatinib 600 mg/day from Day 15 (cohorts 1 and 2) or from Day 1 (cohorts 3 and 4). After hematologic reconstitution after the cytopenic phase, cytarabine was given at a dose of 10 mg/m(2)/day in addition to imatinib as maintenance treatment.

RESULTS:

A total of 16 patients were available for analysis, median age 59 years (range, 37-74). All patients who received more intensive induction treatment (cohorts 3 and 4, n = 7) achieved a hematologic response (HR). In contrast, HR was achieved in only 6 of 9 patients treated in cohorts 1 and 2. The induction treatment was well tolerated. Six patients who achieved HR received an allo-SCT with myeloablative conditioning. The median survival in the transplant group was 16.2 months vs 4.7 months in the group with conventional treatment only (P = .067).

CONCLUSIONS:

The combination of mitoxantrone/etoposide and imatinib is well tolerated, with mild nonhematologic toxicity even in older patients. Eligible patients benefit from allo-SCT after response to the induction treatment.

• Authors: Stefan Fruehauf, Julian Topaly, Eike C Buss, Thomas Fischer, Oliver G Ottmann, Bertold Emmerich, Martin C Müller, Peter Schuld, Leopold Balleisen, Rüdiger Hehlmann, Anthony D Ho, Andreas Hochhaus
• Journal: Cancer (Cancer) Vol. 109 Issue 8 Pg. 1543-9 (Apr 15 2007) ISSN: 0008-543X [Print] United States
• PMID: 17340589 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Piperazines
• Pyrimidines
• Cytarabine
• Etoposide
• Imatinib Mesylate
• Mitoxantrone

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Benzamides
• Blast Crisis (drug therapy, mortality)
• Cytarabine (administration & dosage, adverse effects)
• Etoposide (administration & dosage, adverse effects)
• Female
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, mortality)
• Male
• Middle Aged
• Mitoxantrone (administration & dosage, adverse effects)
• Piperazines (administration & dosage, adverse effects)
• Pyrimidines (administration & dosage, adverse effects)
• Survival Analysis
• Treatment Outcome