Gemtuzumab, fludarabine, cytarabine, and cyclosporine in patients with newly diagnosed acute myelogenous leukemia or high-risk myelodysplastic syndromes.

Abstract

BACKGROUND:

Gemtuzumab is used to treat patients with previously untreated or recurrent acute myelogenous leukemia (AML). The fludarabine and cytarabine (ara-C) regimen is active in these patients. Resistance to gemtuzumab is associated with blast multidrug resistance (MDR). The objectives of this study were to evaluate the efficacy and toxicity of a combination regimen of gemtuzumab, fludarabine, ara-C, and the MDR modifier (cyclosporine [CyA]) in patients with previously untreated AML, refractory anemia with excess blasts (RAEB), or RAEB in transformation (RAEBT).

METHODS:

The MFAC regimen was comprised of gemtuzumab (Mylotarg trade mark ) (6 mg/m(2) intravenously [i.v.] on Day 1); fludarabine and ara-C (15 mg/m(2) and 0.5 g/m(2), respectively, twice daily on Days 2-6); and CSA (6 mg/kg loading dose before gemtuzumab, followed by 16 mg/kg continuous i.v. infusion on Days 1 and 2).

RESULTS:

Fifty-nine evaluable patients were treated: 39 patients (66%) had AML and 20 patients (34%) had RAEB/RAEBT. Their median age was 57 years (range, 27-76 years). The MFAC regimen induced complete remission (CR) in 27 patients (46%) and CR with incomplete platelet recovery (CRp) in 1 patient (2%). The median survival period is 8 months. At 12 months, the survival rate is 38% and the event-free survival rate in patients with CR/CRp is 27%. Infections complicated 38% of the courses of chemotherapy. Grade 3/4 toxicity included hyperbilirubinemia in 31% and transaminitis in 7% of the patients. Four patients (7%) developed hepatic venoocclusive disease (VOD).

CONCLUSIONS:

The MFAC regimen may merit further study in patients with AML if measures to avoid and/or treat VOD can be incorporated into the regimen.

• Authors: Apostolia Tsimberidou, Elihu Estey, Jorge Cortes, Deborah Thomas, Stefan Faderl, Srdan Verstovsek, Guillermo Garcia-Manero, Michael Keating, Maher Albitar, Susan O'Brien, Hagop Kantarjian, Francis Giles
• Journal: Cancer (Cancer) Vol. 97 Issue 6 Pg. 1481-7 (Mar 15 2003) ISSN: 0008-543X [Print] United States
• PMID: 12627513 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11239

Chemical References

• Aminoglycosides
• Anti-Bacterial Agents
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Cytarabine
• Cyclosporine
• Gemtuzumab
• Aspartate Aminotransferases
• Alanine Transaminase
• Vidarabine
• fludarabine

Topics

• Adult
• Aged
• Alanine Transaminase (analysis)
• Aminoglycosides
• Anemia, Refractory, with Excess of Blasts (drug therapy, pathology)
• Anti-Bacterial Agents (administration & dosage)
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Aspartate Aminotransferases (analysis)
• Cyclosporine (administration & dosage)
• Cytarabine (administration & dosage)
• Female
• Gemtuzumab
• Humans
• Hyperbilirubinemia (chemically induced)
• Leukemia, Myeloid, Acute (drug therapy, pathology)
• Male
• Middle Aged
• Survival
• Treatment Outcome
• Vidarabine (administration & dosage, analogs & derivatives)