title: SWOG0919: a Phase 2 study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukaemia.
abstract: Inhibition of cholesterol synthesis and uptake sensitizes acute myeloid leukaemia (AML) blasts to chemotherapy. A Phase 1 study demonstrated the safety of high dose pravastatin given with idarubicin and cytarabine in patients with AML and also demonstrated an encouraging response rate. The Southwestern Oncology Group (SWOG) trial, SWOG S0919, was a Phase 2 trial evaluating the complete remission (CR) rate in a larger number of patients with relapsed AML treated with idarubicin, cytarabine and pravastatin. This study closed to accrual after meeting the defined criterion for a positive study. Thirty-six patients with a median age of 59 years (range 23-78) were enrolled. The median time from diagnosis to registration was 18 months. Relapse status was first relapse, 17 patients (47%); second relapse, 15 patients (42%); third relapse, two patients (5·5%) and fourth relapse, two patients (5·5%). The response rate was 75% [95% confidence interval: 58-88%; 20 CRs, 7 CR with incomplete count recovery (CRi)], and the median overall survival was 12 months. The P-value comparing 75-30% (the null response rate based on prior SWOG experience) was 3·356 × 10(-4) . Given the encouraging CR/CRi rate, this regimen should be considered for testing in a prospective randomized trial against best conventional therapy.
authors.affiliation: Department of Hematologic Oncology and Blood Disorders, The Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Anjali S
authors.initials: AS
authors.lastname: Advani
authors.forename: Shannon
authors.initials: S
authors.lastname: McDonough
authors.forename: Edward
authors.initials: E
authors.lastname: Copelan
authors.forename: Cheryl
authors.initials: C
authors.lastname: Willman
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Mulford
authors.forename: Alan F
authors.initials: AF
authors.lastname: List
authors.forename: Mikkael A
authors.initials: MA
authors.lastname: Sekeres
authors.forename: Megan
authors.initials: M
authors.lastname: Othus
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage / Q000009:adverse effects; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003561:Cytarabine; D017035:Pravastatin; D015255:Idarubicin
keywords: acute myeloid leukaemia; chemotherapy; cholesterol; pravastatin; relapse