RESUMEN
The Therapeutic Intensification in De Novo Leukaemia (TIDEL)-II study enrolled 210 patients with chronic phase chronic myeloid leukemia (CML) in two equal, sequential cohorts. All started treatment with imatinib 600 mg/day. Imatinib plasma trough level was performed at day 22 and if <1000 ng/mL, imatinib 800 mg/day was given. Patients were then assessed against molecular targets: BCR-ABL1 ≤10%, ≤1%, and ≤0.1% at 3, 6, and 12 months, respectively. Cohort 1 patients failing any target escalated to imatinib 800 mg/day, and subsequently switched to nilotinib 400 mg twice daily for failing the same target 3 months later. Cohort 2 patients failing any target switched to nilotinib directly, as did patients with intolerance or loss of response in either cohort. At 2 years, 55% of patients remained on imatinib, and 30% on nilotinib. Only 12% were >10% BCR-ABL1 at 3 months. Confirmed major molecular response was achieved in 64% at 12 months and 73% at 24 months. MR4.5 (BCR-ABL1 ≤0.0032%) at 24 months was 34%. Overall survival was 96% and transformation-free survival was 95% at 3 years. This trial supports the feasibility and efficacy of an imatinib-based approach with selective, early switching to nilotinib. This trial was registered at www.anzctr.org.au as #12607000325404.
Asunto(s)
Benzamidas/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Benzamidas/administración & dosificación , Benzamidas/efectos adversos , Femenino , Proteínas de Fusión bcr-abl/análisis , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
We evaluated the effect of adjuvant whole brain irradiation (WBI) after surgery or radiosurgery for solitary brain metastases in a Phase III multicentre trial with randomization to 30-36 Gy WBI or observation. The study was closed early due to slow accrual after 19 patients (WBI 10, observation 9). There was no difference in CNS failure-free survival or overall survival between the arms. There was a trend to reduced CNS relapse with WBI (30% versus 78%, P=0.12). Limited analysis of quality of life and neurocognitive function data revealed no evidence of difference between the arms. Our results are not inconsistent with two larger randomized trials and support the use of upfront WBI to decrease brain recurrence in this setting.