A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older.
This phase 3, multicenter, open-label study evaluated the efficacy and safety of tipifarnib compared with best supportive care (BSC), including hydroxyurea, as first-line therapy in elderly patients (>or=70 years) with newly diagnosed, de novo, or secondary acute myeloid leukemia. A total of 457 patients were enrolled with 24% 80 years of age or older. Tipifarnib 600 mg orally twice a day was administered for the first 21 consecutive days, in 28-day cycles. The primary endpoint was overall survival. The median survival was 107 days for the tipifarnib arm and 109 days for the BSC arm. The hazard ratio (tipifarnib vs BSC) for overall survival was 1.02 (P value by stratified log-rank test, .843). The complete response rate for tipifarnib in this study (8%) was lower than that observed previously, but with a similar median duration of 8 months. The most frequent grade 3 or 4 adverse events were cytopenias in both arms, slightly more infections (39% vs 33%), and febrile neutropenia (16% vs 10%) seen in the tipifarnib arm. The results of this randomized study showed that tipifarnib treatment did not result in an increased survival compared with BSC, including hydroxyurea. This trial was registered at www.clinicaltrials.gov as #NCT00093990.
Harousseau
Jean-Luc
JL
University Hospital Hotel-Dieu, Nantes, France. jl-harousseau@nantes.fnclcc.fr
Martinelli
Giovanni
G
Jedrzejczak
Wieslaw W
WW
Brandwein
Joseph M
JM
Bordessoule
Dominique
D
Masszi
Tamas
T
Ossenkoppele
Gert J
GJ
Alexeeva
Julia A
JA
Beutel
Gernot
G
Maertens
Johan
J
Vidriales
Maria-Belen
MB
Dombret
Hervé
H
Thomas
Xavier
X
Burnett
Alan K
AK
Robak
Tadeusz
T
Khuageva
Nuriet K
NK
Golenkov
Anatoly K
AK
Tothova
Elena
E
Mollgard
Lars
L
Park
Youn C
YC
Bessems
Annick
A
De Porre
Peter
P
Howes
Angela J
AJ
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage* / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D015363:Quinolones / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate; D013997:Time Factors
D000970:Antineoplastic Agents; D015363:Quinolones; C402769:tipifarnib; D006918:Hydroxyurea