P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808.
Cancer and Leukemia Group B 19808 (CALGB 19808) is the only randomized trial of a second-generation P-glycoprotein (Pgp) modulator in untreated patients with acute myeloid leukemia (AML) younger than age 60 years. We randomly assigned 302 patients to receive induction chemotherapy regimens consisting of cytosine arabinoside (Ara-C; A), daunorubicin (D), and etoposide (E), without (ADE) or with (ADEP) PSC-833 (P). The incidence of complete remission was 75% with both regimens. Reversible grade 3 and 4 liver and mucosal toxicities were significantly more common with ADEP. Therapy-related mortality was 7% and did not differ by induction arm. Excess cardiotoxicity was not seen with high doses of D in ADE. The median disease-free survival was 1.34 years in the ADE arm and 1.09 years in the ADEP arm (P = .74, log-rank test); the median overall survival was 1.86 years in the ADE arm and 1.69 years in the ADEP arm (P = .82). There was no evidence of a treatment difference within any identifiable patient subgroup. Inhibition of Pgp-mediated drug efflux by PSC-833 did not improve clinical outcomes in younger patients with untreated AML. This trial was registered at www.clinicaltrials.gov as #NCT00006363.
North Shore University Hospital, Hofstra University School of Medicine, Lake Success, NY 11042, USA. kolitz@nshs.edu
Jonathan E
JE
Kolitz
Stephen L
SL
George
Guido
G
Marcucci
Ravi
R
Vij
Bayard L
BL
Powell
Steven L
SL
Allen
Daniel J
DJ
DeAngelo
Thomas C
TC
Shea
Wendy
W
Stock
Maria R
MR
Baer
Vera
V
Hars
Kati
K
Maharry
Eva
E
Hoke
James W
JW
Vardiman
Clara D
CD
Bloomfield
Richard A
RA
Larson
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003524:Cyclosporins / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D003561:Cytarabine; D005047:Etoposide; C070272:valspodar; D003630:Daunorubicin