Phase II trial of tipifarnib as maintenance therapy in first complete remission in adults with acute myelogenous leukemia and poor-risk features.
OBJECTIVE
Acute myelogenous leukemia (AML) does not have a high cure rate, particularly in patients with poor-risk features. Such patients might benefit from additional therapy in complete remission (CR). Tipifarnib is an oral farnesyltransferase inhibitor with activity in AML. We conducted a phase II trial of maintenance tipifarnib monotherapy for 48 adults with poor-risk AML in first CR.


METHODS
Tipifarnib 400 mg twice daily for 14 of 21 days was initiated after recovery from consolidation chemotherapy, for a maximum of 16 cycles (48 weeks).


RESULTS
Twenty (42%) patients completed 16 cycles, 24 (50%) were removed from study for relapse, and 4 (8%) discontinued drug prematurely for intolerance. Nonhematologic toxicities were rare, but tipifarnib dose was reduced in 58% for myelosuppression. Median disease-free survival (DFS) was 13.5 months (range, 3.5-59+ months), with 30% having DFS >2 years. Comparison of CR durations for 25 patients who received two-cycle timed sequential therapy followed by tipifarnib maintenance with 23 historically similar patients who did not receive tipifarnib showed that tipifarnib was associated with DFS prolongation for patients with secondary AML and adverse cytogenetics.


CONCLUSIONS
This study suggests that some patients with poor-risk AML, including patients with secondary AML and adverse cytogenetics, may benefit from tipifarnib maintenance therapy. Future studies are warranted to examine alternative tipifarnib dosing and continuation beyond 16 cycles.
Karp
Judith E
JE
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231-1000, USA. jkarp2@jhmi.edu
Smith
B Douglas
BD
Gojo
Ivana
I
Lancet
Jeffrey E
JE
Greer
Jacqueline
J
Klein
Maureen
M
Morris
Larry
L
Levis
Mark J
MJ
Gore
Steven D
SD
Wright
John J
JJ
Garrett-Mayer
Elizabeth
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000627:therapeutic use*; D012074:Remission Induction; D012307:Risk Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015363:Quinolones; C402769:tipifarnib