Clofarabine, cyclophosphamide and etoposide for the treatment of relapsed or resistant acute leukemia in pediatric patients.

Abstract

Clofarabine is a promising new chemotherapeutic agent that is active in the treatment of pediatric acute leukemia. Forty children (16 with acute myeloid leukemia [AML], 24 with acute lymphoblastic leukemia [ALL]), aged 1-20 years (median 7.6 years) with relapsed or refractory ALL or AML were treated because of resistance to first-line treatment (n =5), or for first (n =22), second (n =11) or third relapse (n =2). They received clofarabine (40 mg/m(2)/day) associated with etoposide (100 mg/m(2)/day) and cyclophosphamide (440 mg/m(2)/day) administered as one or two induction cycles (5 days of chemotherapy) in an attempt to reach complete remission (CR) or CR without platelet recovery (CRp). This was followed by 1-3 consolidation cycles (4 days of chemotherapy) for a maximum of four cycles. Seven (44%) out of 16 and 10 (42%) out of 24 evaluable children with AML and ALL, respectively, responded to treatment. The most common adverse events were infections and gastrointestinal and hepatic toxicity. Thirteen (76%) out of 17 responders underwent hematopoietic stem cell transplant. The 24-month overall survival was 25%, while it was 59% among patients who responded to the first induction cycle. Our study suggests that this drug regimen is well tolerated and can be effective in heavily pretreated pediatric patients with relapsed or refractory acute leukemia.

• Authors: Maurizio Miano, Angela Pistorio, Maria C Putti, Carlo Dufour, Chiara Messina, Elena Barisone, Ottavio Ziino, Rosanna Parasole, Matteo Luciani, Luca Lo Nigro, Giulio De Rossi, Stefania Varotto, Nicoletta Bertorello, Fara Petruzziello, Michaela Calvillo, Concetta Micalizzi
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 53 Issue 9 Pg. 1693-8 (Sep 2012) ISSN: 1029-2403 [Electronic] United States
• PMID: 22303898 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Adenine Nucleotides
• Arabinonucleosides
• Etoposide
• Clofarabine
• Cyclophosphamide

Topics

• Acute Disease
• Adenine Nucleotides (administration & dosage, adverse effects)
• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Arabinonucleosides (administration & dosage, adverse effects)
• Chemical and Drug Induced Liver Injury (etiology)
• Child
• Child, Preschool
• Clofarabine
• Cyclophosphamide (administration & dosage, adverse effects)
• Drug Administration Schedule
• Etoposide (administration & dosage, adverse effects)
• Female
• Gastrointestinal Diseases (chemically induced)
• Humans
• Infant
• Kaplan-Meier Estimate
• Leukemia, Myeloid (drug therapy, pathology)
• Male
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, pathology)
• Prospective Studies
• Recurrence
• Remission Induction
• Treatment Outcome