Division of Hematology and Oncology, The Ohio State University, Center for Biostatistics, The Ohio State University, Columbus, OH 43210, USA.
J Clin Oncol. 2010 Jan 20;28(3):418-23. doi: 10.1200/JCO.2009.24.1570. Epub 2009 Dec 14.
Flavopiridol downmodulates antiapoptotic proteins associated with resistance to fludarabine and rituximab and is effective against p53-mutated chronic lymphocytic leukemia (CLL). We conducted a phase I study of flavopiridol, fludarabine, and rituximab (FFR) in patients with mantle-cell lymphoma (MCL), indolent B-cell non-Hodgkin's lymphomas (B-NHL), and CLL to determine the activity of FFR.
Therapy included fludarabine 25 mg/m(2) intravenously (IV) days 1 to 5 and rituximab 375 mg/m(2) day 1 every 28 days for 6 cycles. We administered flavopiridol 50 mg/m(2) by 1-hour IV bolus (IVB) day 1 (n = 15); day 1 to 2 (n = 6); 20 mg/m(2) 30-minute IVB + 20 mg/m(2) 4-hour IV infusion (n = 3); or 30 mg/m(2) + 30 mg/m(2) (n = 14).
Thirty-eight patients (median age, 62 years) with MCL (n = 10); indolent B-NHL including follicular (n = 9), marginal zone (n = 4), lymphoplasmacytic (n = 1), or small lymphocytic lymphoma (n = 3); and CLL (n = 11), were enrolled. Twenty-two patients were previously untreated; 16 had received one to two prior therapies. Two patients in cohort 2 developed grade 3 dose-limiting toxicity (seizures, renal insufficiency). The median number of treatment cycles was 4, with cytopenias (n = 10) and fatigue (n = 3) the most common reasons for early discontinuation. Overall response rate was 82% (complete response, 50%; unconfirmed complete response, 5%; partial response, 26%), including 80% of patients with MCL (median age, 68; seven complete responses, one partial response). Median progression-free survival (PFS) was 25.6 months. Median PFS of patients with nonblastoid variant MCL (n = 8) was 35.9 months.
FFR was active in MCL, indolent B-NHL, and CLL and should be studied for older patients with MCL who are not candidates for aggressive chemotherapy.
Flavopiridol 下调与氟达拉滨和利妥昔单抗耐药相关的抗凋亡蛋白，对 p53 突变的慢性淋巴细胞白血病（CLL）有效。我们在套细胞淋巴瘤（MCL）、惰性 B 细胞非霍奇金淋巴瘤（B-NHL）和 CLL 患者中进行了 flavopiridol、氟达拉滨和利妥昔单抗（FFR）的 I 期研究，以确定 FFR 的活性。
治疗包括氟达拉滨 25mg/m2 静脉内（IV）滴注（n = 15）；第 1 天至第 2 天（n = 6）；20mg/m2 30 分钟 IVB + 20mg/m2 4 小时 IV 输注（n = 3）；或 30mg/m2 + 30mg/m2（n = 14）。
38 例患者（中位年龄 62 岁），其中 MCL（n = 10）；惰性 B-NHL 包括滤泡性（n = 9）、边缘区（n = 4）、淋巴浆细胞性（n = 1）或小淋巴细胞性淋巴瘤（n = 3）；和 CLL（n = 11）。22 例患者为初治患者；16 例患者接受了 1 至 2 种先前的治疗。第 2 队列的 2 例患者发生了 3 级剂量限制性毒性（癫痫发作，肾功能不全）。中位治疗周期数为 4 个，最常见的早期停药原因是血细胞减少（n = 10）和疲劳（n = 3）。总缓解率为 82%（完全缓解，50%；未确认的完全缓解，5%；部分缓解，26%），包括 80%的 MCL 患者（中位年龄 68 岁；7 例完全缓解，1 例部分缓解）。中位无进展生存期（PFS）为 25.6 个月。非母细胞变异型 MCL 患者（n = 8）的中位 PFS 为 35.9 个月。
FFR 在 MCL、惰性 B-NHL 和 CLL 中具有活性，应在不适合积极化疗的老年 MCL 患者中进行研究。
