BACKGROUND: The authors conducted a phase 1/2 study of tipifarnib in combination with idarubicin and cytarabine (IA) in 95 patients with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome. METHODS: Induction consisted of idarubicin 12 mg/m(2) a day on days 1-3, cytarabine 1.5 g/m(2) intravenously continuously daily on days 1-4 (days 1-3 if age ≥60 years), and tipifarnib, with the first cohort (n = 6) receiving 200 mg orally twice a day and all others receiving 300 mg twice a day for 21 days every 28 days. Consolidation consisted of 5 courses of idarubicin 8 mg/m(2) a day on days 1-2, cytarabine 0.75 g/m(2) a day on days 1-3, and tipifarnib 300 mg twice a day for 14 days every 4-6 weeks. Maintenance with tipifarnib 300 mg twice a day for 21 days every 4-6 weeks was continued for 6 months. RESULTS: With a median follow-up of 33 months, 61 patients achieved complete remission (CR) (64%), and 9 achieved complete remission with incomplete platelet recovery (CRp) (9%). The median duration of CR was not reached. Median overall survival was 17 months. The most common grade 3 adverse events were gastrointestinal toxicities, liver dysfunction, and skin rash. Compared with historical IA, IA and tipifarnib showed a better CR duration (P = .04) and a trend toward a higher CR rate in patients with chromosome 5/7 abnormalities. CONCLUSIONS: The combination of IA and tipifarnib is safe and active. Further studies exploring different dosages and schedules are warranted, particularly in patients with poor-risk AML.
BACKGROUND: The authors conducted a phase 1/2 study of tipifarnib in combination with idarubicin and cytarabine (IA) in 95 patients with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome. METHODS: Induction consisted of idarubicin 12 mg/m(2) a day on days 1-3, cytarabine 1.5 g/m(2) intravenously continuously daily on days 1-4 (days 1-3 if age ≥60 years), and tipifarnib, with the first cohort (n = 6) receiving 200 mg orally twice a day and all others receiving 300 mg twice a day for 21 days every 28 days. Consolidation consisted of 5 courses of idarubicin 8 mg/m(2) a day on days 1-2, cytarabine 0.75 g/m(2) a day on days 1-3, and tipifarnib 300 mg twice a day for 14 days every 4-6 weeks. Maintenance with tipifarnib 300 mg twice a day for 21 days every 4-6 weeks was continued for 6 months. RESULTS: With a median follow-up of 33 months, 61 patients achieved complete remission (CR) (64%), and 9 achieved complete remission with incomplete platelet recovery (CRp) (9%). The median duration of CR was not reached. Median overall survival was 17 months. The most common grade 3 adverse events were gastrointestinal toxicities, liver dysfunction, and skin rash. Compared with historical IA, IA and tipifarnib showed a better CR duration (P = .04) and a trend toward a higher CR rate in patients with chromosome 5/7 abnormalities. CONCLUSIONS: The combination of IA and tipifarnib is safe and active. Further studies exploring different dosages and schedules are warranted, particularly in patients with poor-risk AML.
Authors: D W End; G Smets; A V Todd; T L Applegate; C J Fuery; P Angibaud; M Venet; G Sanz; H Poignet; S Skrzat; A Devine; W Wouters; C Bowden Journal: Cancer Res Date: 2001-01-01 Impact factor: 12.701
Authors: P Greenberg; C Cox; M M LeBeau; P Fenaux; P Morel; G Sanz; M Sanz; T Vallespi; T Hamblin; D Oscier; K Ohyashiki; K Toyama; C Aul; G Mufti; J Bennett Journal: Blood Date: 1997-03-15 Impact factor: 22.113
Authors: J E Karp; J E Lancet; S H Kaufmann; D W End; J J Wright; K Bol; I Horak; M L Tidwell; J Liesveld; T J Kottke; D Ange; L Buddharaju; I Gojo; W E Highsmith; R T Belly; R J Hohl; M E Rybak; A Thibault; J Rosenblatt Journal: Blood Date: 2001-06-01 Impact factor: 22.113
Authors: Razelle Kurzrock; Hagop M Kantarjian; Jorge E Cortes; Neil Singhania; Deborah A Thomas; Edward F Wilson; John J Wright; Emil J Freireich; Moshe Talpaz; Saïd M Sebti Journal: Blood Date: 2003-08-28 Impact factor: 22.113
Authors: Thomas E Witzig; Hui Tang; Ivana N M Micallef; Stephen M Ansell; Brian K Link; David J Inwards; Luis F Porrata; Patrick B Johnston; Joseph P Colgan; Svetomir N Markovic; Grzegorz S Nowakowski; Carrie A Thompson; Cristine Allmer; Matthew J Maurer; Mamta Gupta; George Weiner; Ray Hohl; Paul J Kurtin; Husheng Ding; David Loegering; Paula Schneider; Kevin Peterson; Thomas M Habermann; Scott H Kaufmann Journal: Blood Date: 2011-07-01 Impact factor: 22.113
Authors: Katarzyna Krzykowska-Petitjean; Jędrzej Małecki; Anna Bentke; Barbara Ostrowska; Piotr Laidler Journal: J Cancer Res Clin Oncol Date: 2011-12-31 Impact factor: 4.553