Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia.
Flavopiridol, a cyclin-dependent kinase inhibitor, is cytotoxic to leukemic blasts. In a Phase II study, flavopiridol 50 mg/m(2) was given by 1-h infusion daily x 3 beginning day 1 followed by 2 g/m(2)/72 h ara-C beginning day 6 and 40 mg/m(2) mitoxantrone on day 9 (FLAM) to 45 adults with newly diagnosed acute myelogenous leukemia (AML) with multiple poor-risk features. Thirty patients (67%) achieved complete remission (CR) and 4 (9%) died. Twelve (40%) received myeloablative allogeneic bone marrow transplant (BMT) in first CR. Median OS and DFS are not reached (67% alive 12.5-31 months, 58% in CR 11.4-30 months), with median follow-up 22 months. Sixteen received FLAM in CR, with median OS and DFS 9 and 13.1 months, and 36% alive at 21-31 months. Short OS and DFS correlated with adverse cytogenetics, regardless of age or treatment in CR. The addition of allogeneic BMT in CR translates into long OS and DFS in the majority of eligible patients.
Karp
Judith E
JE
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231-1000, USA. jkarp2@jhmi.edu
Blackford
Amanda
A
Smith
B Douglas
BD
Alino
Katrina
K
Seung
Amy Hatfield
AH
Bolaños-Meade
Javier
J
Greer
Jacqueline M
JM
Carraway
Hetty E
HE
Gore
Steven D
SD
Jones
Richard J
RJ
Levis
Mark J
MJ
McDevitt
Michael A
MA
Doyle
L Austin
LA
Wright
John J
JJ
D000328:Adult; D000368:Aged; D000493:Allopurinol / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced / Q000517:prevention & control; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D011073:Polyamines / Q000627:therapeutic use; D011292:Premedication; D012074:Remission Induction; D012306:Risk; D018805:Sepsis / Q000209:etiology / Q000401:mortality; D000069603:Sevelamer; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D015275:Tumor Lysis Syndrome / Q000209:etiology / Q000517:prevention & control; D055815:Young Adult
D005419:Flavonoids; D010880:Piperidines; D011073:Polyamines; D003561:Cytarabine; C077990:alvocidib; D000493:Allopurinol; D000069603:Sevelamer; D008942:Mitoxantrone