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


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%).


CONCLUSIONS
The addition of amifostine does not allow dose escalation of idarubicin when combined with high-dose ara-C.
Garcia-Manero
Guillermo
G
Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX 77030, USA. ggarciam@mdanderson.org
Faderl
Stefan
S
Giles
Francis
F
Thomas
Deborah
D
Cortes
Jorge
J
O'Brien
Susan
S
Davis
Jan
J
Kantarjian
Hagop M
HM
Estey
Elihu
E
D000328:Adult; D004999:Amifostine / Q000008:administration & dosage / Q000009:adverse effects; D000754:Anemia, Refractory, with Excess of Blasts / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D016896:Treatment Outcome
D003561:Cytarabine; D004999:Amifostine; D015255:Idarubicin