le Coutre Philipp, Ottmann Oliver G, Giles Francis, Kim Dong-Wook, Cortes Jorge, Gattermann Norbert, Apperley Jane F, Larson Richard A, Abruzzese Elisabetta, O'Brien Stephen G, Kuliczkowski Kazimierz, Hochhaus Andreas, Mahon Francois-Xavier, Saglio Giuseppe, Gobbi Marco, Kwong Yok-Lam, Baccarani Michele, Hughes Timothy, Martinelli Giovanni, Radich Jerald P, Zheng Ming, Shou Yaping, Kantarjian Hagop
Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Germany.
Blood. 2008 Feb 15;111(4):1834-9. doi: 10.1182/blood-2007-04-083196. Epub 2007 Nov 29.
Patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia (CML-AP) have very limited therapeutic options. Nilotinib is a highly selective BCR-ABL tyrosine kinase inhibitor. This phase 2 trial was designed to characterize the efficacy and safety of nilotinib (400 mg twice daily) in this patient population with hematologic response (HR) as primary efficacy endpoint. A total of 119 patients were enrolled and had a median duration of treatment of 202 days (range, 2-611 days). An HR was observed in 56 patients (47%; 95% confidence interval [CI], 38%-56%). Major cytogenetic response (MCyR) was observed in 35 patients (29%; 95% CI, 21%-39%). The median duration of HR has not been reached. Overall survival rate among the 119 patients after 12 months of follow-up was 79% (95% CI, 70%-87%). Nonhematologic adverse events were mostly mild to moderate. Severe peripheral edema and pleural effusions were not observed. The most common grade 3 or higher hematologic adverse events were thrombocytopenia (35%) and neutropenia (21%). Grade 3 or higher bilirubin and lipase elevations occurred in 9% and 18% of patients, respectively, resulting in treatment discontinuation in one patient. In conclusion, nilotinib is an effective and well-tolerated treatment in imatinib-resistant and -intolerant CML-AP. This trial is registered at www.clinicaltrials.gov as NCT00384228.
对伊马替尼耐药或不耐受的加速期慢性粒细胞白血病（CML-AP）患者的治疗选择非常有限。尼洛替尼是一种高度选择性的BCR-ABL酪氨酸激酶抑制剂。这项2期试验旨在以血液学缓解（HR）作为主要疗效终点，评估尼洛替尼（每日两次，每次400mg）在该患者群体中的疗效和安全性。共纳入119例患者，中位治疗持续时间为202天（范围2-611天）。56例患者（47%；95%置信区间[CI]，38%-56%）观察到血液学缓解。35例患者（29%；95%CI，21%-39%）观察到主要细胞遗传学缓解（MCyR）。HR的中位持续时间尚未达到。119例患者随访12个月后的总生存率为79%（95%CI，70%-87%）。非血液学不良事件大多为轻至中度。未观察到严重外周水肿和胸腔积液。最常见的3级或更高等级血液学不良事件为血小板减少症（35%）和中性粒细胞减少症（21%）。分别有9%和18%的患者出现3级或更高等级胆红素和脂肪酶升高，导致1例患者停药。总之, 尼洛替尼是治疗伊马替尼耐药和不耐受CML-AP的一种有效且耐受性良好 的药物。该试验已在www.clinicaltrials.gov注册，注册号为NCT00384228。
