A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia.
This phase 2 study evaluated the efficacy and safety of the oral farnesyltransferase inhibitor tipifarnib in adults with refractory or relapsed acute myeloid leukemia (AML). Patients (n=252) received tipifarnib 600 mg twice a day for 21 days in 28-day cycles. Median age was 62 years; 99 (39%) patients were 65 years or older. Eleven (4%) of 252 patients achieved complete remission (CR) or complete remission with incomplete platelet recovery (CRp; 9 CR and 2 CRp). Nineteen patients (8%), including those who achieved CR/CRp, achieved a reduction in bone marrow blasts to less than 5% blasts. Bone marrow blasts were reduced more than 50% in an additional 8 patients (total = 27; 11%). Median survival was 369 days for patients who achieved CR/CRp. Myelosuppression was the most common adverse event. The most common nonhematologic toxicities were fever, nausea, and hypokalemia. Single-agent treatment with tipifarnib induced durable CR/CRp, which was associated with prolonged survival, in some patients with refractory or relapsed AML. The response rate observed in this heavily pretreated group of patients suggests the requirement to enhance the response rate either by combining tipifarnib with other active agents or determining factors that are predictive of response.
Harousseau
Jean-Luc
JL
Service d'Hématologie, Hôtel Dieu, Nantes, France. jean-luc.harousseau@univ-nantes.fr
Lancet
Jeffrey E
JE
Reiffers
Josy
J
Lowenberg
Bob
B
Thomas
Xavier
X
Huguet
Francoise
F
Fenaux
Pierre
P
Zhang
Steven
S
Rackoff
Wayne
W
De Porre
Peter
P
Stone
Richard
R
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001752:Blast Crisis / Q000473:pathology / Q000517:prevention & control; D001854:Bone Marrow Cells / Q000473:pathology; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D012074:Remission Induction / Q000379:methods; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods*; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015363:Quinolones; D051231:Farnesyltranstransferase; C402769:tipifarnib