A phase I study of idarubicin dose escalation with amisfostine and high-dose cytarabine in patients with relapsed acute myelogenous leukemia and myelodysplastic syndromes.

Abstract

BACKGROUND AND OBJECTIVES:

Early studies have suggested that increasing doses of anthracycline improve outcome in younger patients with acute myelogenous leukemia (AML), but dose escalation has been precluded by the acute and chronic toxicities of these agents. Amifostine is a cytoprotective compound that has been shown to protect against the acute cytotoxicities of anthracyclines in animal models. We report the results of a phase I study of dose escalation of idarubicin with amifostine and high-dose ara-C in patients with relapsed or refractory AML or myelodysplastic syndrome (MDS).

DESIGN AND METHODS:

The continuous reassessment method was used to predict the probability of toxicity.

RESULTS:

Five patients were treated at an idarubicin dose of 18 mg/m2/day x 3, three of whom developed grade 3 diarrhea or mucositis. Subsequently, three additional patients were treated at a dose of 15 mg/m2 x 3 days, all of whom experienced grade 3 diarrhea or mucositis. One patient achieved complete remission (CR rate 12.5%, 95% CI 0-0.52%).

INTERPRETATION AND CONCLUSIONS:

The addition of amifostine does not allow dose escalation of idarubicin when combined with high-dose ara-C.

• Authors: Guillermo Garcia-Manero, Stefan Faderl, Francis Giles, Deborah Thomas, Jorge Cortes, Susan O'Brien, Jan Davis, Hagop M Kantarjian, Elihu Estey
• Journal: Haematologica (Haematologica) Vol. 87 Issue 8 Pg. 804-7 (Aug 2002) ISSN: 0390-6078 [Print] Italy
• PMID: 12161355 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• Cytarabine
• Amifostine
• Idarubicin

Topics

• Adult
• Amifostine (administration & dosage, adverse effects)
• Anemia, Refractory, with Excess of Blasts (drug therapy)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Cardiovascular Diseases (chemically induced)
• Cytarabine (administration & dosage, adverse effects)
• Diarrhea (chemically induced)
• Dose-Response Relationship, Drug
• Female
• Humans
• Idarubicin (administration & dosage, adverse effects)
• Leukemia, Myeloid (drug therapy)
• Male
• Middle Aged
• Recurrence
• Remission Induction
• Salvage Therapy
• Treatment Outcome