Nilotinib has a higher binding affinity and selectivity for BCR-ABL with respect to imatinib and is an effective treatment of chronic myeloid leukemia (CML) after imatinib failure. In a phase 2 study, 73 early chronic-phase, untreated, Ph(+) CML patients, received nilotinib at a dose of 400 mg twice daily. The primary endpoint was the complete cytogenetic response (CCgR) rate at 1 year. With a median follow-up of 15 months, the CCgR rate at 1 year was 96%, and the major molecular response rate 85%. Responses were rapid, with 78% CCgR and 52% major molecular response at 3 months. During the first year, the treatment was interrupted at least once in 38 patients (52%). The mean daily dose ranged between 600 and 800 mg in 74% of patients, 400 and 599 mg in 18% of patients, and was less than 400 mg in 8% of patients. Dose interruptions were mainly due to nonhematologic and biochemical side effects. Myelosuppression was irrelevant. One patient progressed to blastic crisis after 6 months; one went off-treatment for lipase increase grade 4 (no pancreatitis). Nilotinib is safe and very active in early chronic-phase CML. These data support a role for nilotinib for the frontline treatment of CML. This study was registered at ClinicalTrials.gov as NCT00481052.
Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia / Rosti G; Palandri F; Castagnetti F; Breccia M; Levato L; Gugliotta G; Capucci A; Cedrone M; Fava C; Intermesoli T; Cambrin GR; Stagno F; Tiribelli M; Amabile M; Luatti S; Poerio A; Soverini S; Testoni N; Martinelli G; Alimena G; Pane F; Saglio G; Baccarani M; GIMEMA CML Working Party.. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 114:24(2009), pp. 4933-4938. [10.1182/blood-2009-07-232595]
Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia.
ROSTI, GIANANTONIO;PALANDRI, FRANCESCA;CASTAGNETTI, FAUSTO;GUGLIOTTA, GABRIELE;AMABILE, MARILINA;LUATTI, SIMONA;POERIO, ANGELA;SOVERINI, SIMONA;TESTONI, NICOLETTA;MARTINELLI, GIOVANNI;BACCARANI, MICHELE;
2009
Abstract
Nilotinib has a higher binding affinity and selectivity for BCR-ABL with respect to imatinib and is an effective treatment of chronic myeloid leukemia (CML) after imatinib failure. In a phase 2 study, 73 early chronic-phase, untreated, Ph(+) CML patients, received nilotinib at a dose of 400 mg twice daily. The primary endpoint was the complete cytogenetic response (CCgR) rate at 1 year. With a median follow-up of 15 months, the CCgR rate at 1 year was 96%, and the major molecular response rate 85%. Responses were rapid, with 78% CCgR and 52% major molecular response at 3 months. During the first year, the treatment was interrupted at least once in 38 patients (52%). The mean daily dose ranged between 600 and 800 mg in 74% of patients, 400 and 599 mg in 18% of patients, and was less than 400 mg in 8% of patients. Dose interruptions were mainly due to nonhematologic and biochemical side effects. Myelosuppression was irrelevant. One patient progressed to blastic crisis after 6 months; one went off-treatment for lipase increase grade 4 (no pancreatitis). Nilotinib is safe and very active in early chronic-phase CML. These data support a role for nilotinib for the frontline treatment of CML. This study was registered at ClinicalTrials.gov as NCT00481052.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
