Department of Hematology-Oncology, L. and A. Seràgnoli, University of Bologna, S. Orsola-Malpighi Hospital, 40138 Bologna, Italy.
Blood. 2009 Dec 3;114(24):4933-8. doi: 10.1182/blood-2009-07-232595. Epub 2009 Oct 12.
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.
尼洛替尼与伊马替尼相比，对 BCR-ABL 具有更高的结合亲和力和选择性，是伊马替尼治疗失败后的慢性髓性白血病（CML）的有效治疗方法。在一项 2 期研究中，73 例早期慢性期、未经治疗、Ph(+)CML 患者接受尼洛替尼 400mg，每日 2 次。主要终点是 1 年时的完全细胞遗传学缓解（CCgR）率。中位随访 15 个月时，1 年时的 CCgR 率为 96%，主要分子学缓解率为 85%。反应迅速，3 个月时 CCgR 率为 78%，主要分子学缓解率为 52%。在第一年中，38 例患者（52%）至少中断过一次治疗。74%的患者平均每日剂量在 600-800mg 之间，18%的患者在 400-599mg 之间，8%的患者低于 400mg。剂量中断主要是由于非血液学和生化副作用。骨髓抑制与治疗无关。1 例患者在 6 个月后进展为成髓细胞危象，1 例患者因脂肪酶升高 4 级（无胰腺炎）停药。尼洛替尼在早期慢性期 CML 中安全且非常有效。这些数据支持尼洛替尼在 CML 一线治疗中的作用。该研究在 ClinicalTrials.gov 上注册为 NCT00481052。
