Acute hematologic toxicity and practicability of dose-intensified BEACOPP chemotherapy for advanced stage Hodgkin's disease
Acute hematologic toxicity and practicability of dose-intensified BEACOPP chemotherapy for advanced stage Hodgkin's disease
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DOI：
10.1023/a:1008301225839
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发表时间：
2000-09-01
影响因子：
50.5
通讯作者：
Diehl, V
中科院分区：
文献类型：
--
作者：
Engel, C;Loeffler, M;Diehl, V
背景资料：最近越来越多的证据表明，新型BEACOPP（博来霉素（B）、依托泊苷（E）、阿霉素（A）、环磷酰胺（C）、长春新碱（O）、甲基苄肼（P）、泼尼松（P））化疗是治疗晚期霍奇金病的高效治疗方法。BEACOPP的两种剂量变体目前正在GHSG的III期随机多中心试验中进行测试。为了使更广泛的测试BEACOPP，我们的特点是其实用性的时间表遵守，急性血液毒性和需要支持treatment.Patients和方法：数据858例（6592治疗周期）从184个参与机构进行了评估。基线变体（第1组）的计划总药物剂量分别为B、E、A、C、O、P和P的80、2400、200、5200、11.2、5600和4480 mg/m2。与组1相比，使用G-CSF辅助，剂量强化变体（组2）中E、A和C的剂量分别递增2.0、1.4、1.92倍。如果出现剂量限制性毒性，则规定逐步减量。这两种变体在八个三周courses.Results：中位剂量依从性（剂量实际上相对于计划的手臂1剂量）在手臂1是1.0的所有药物。第2组中实际维持的E、A和C的相对剂量递增分别为1.83、1.37和1.77（中位数），70%的患者在整个治疗期间维持较高的剂量水平。第2组中25%的周期发生剂量限制性毒性，最常见的是白细胞减少症和血小板减少症。与第1组相比，第2组中白细胞的时间进程显示白细胞减少症更严重，但时间不更长。在所有周期中，WHO 3-4级感染的发生率分别为2.1%（第1组）和3.1%（第2组）。红细胞输注率分别为6%（第1组）和28%（第2组），血小板输注率< 1%（第1组）和6%（第2组）。尽管血液毒性增加，但中度剂量递增对大多数G-CSF辅助和标准支持治疗的患者是安全的。
Background: Evidence is recently accumulating that the novel BEACOPP (bleomycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C), vincristine (O), procarbazine (P), prednisone (P)) chemotherapy is a highly effective treatment for advanced stage Hodgkin's disease. Two dose variants of BEACOPP are currently tested in a phase III randomized multicenter trial of the GHSG. To enable more extensive testing of BEACOPP we characterized its practicability regarding schedule adherence, acute hematotoxicity and need for supportive treatment.Patients and methods: Data of 858 patients (6592 therapy cycles) from 184 participating institutions were evaluated. Planned total drug doses of the baseline variant (arm 1) were 80, 2400, 200, 5200, 11.2, 5600 and 4480 mg/m(2) for B, E, A, C, O, P and P, respectively. Compared to arm 1, the doses of E, A and C in the dose-intensified variant (arm 2) were escalated by factor 2.0, 1.4, 1.92, respectively, using G-CSF assistance. Stepwise dose reductions were specified in case of dose-limiting toxicities. Both variants are given in eight three-weekly courses.Results: Median dose adherence (dose actually given relative to planned arm 1 dose) in arm 1 was 1.0 for all drugs. Relative dose escalation of E, A, and C actually maintained in arm 2 was 1.83, 1.37 and 1.77 (medians), respectively, and 70% of patients maintained elevated dose levels throughout the entire treatment. Dose-limiting toxicities occurred in 25% of cycles in arm 2, most frequently due to leukocytopenia and thrombocytopenia. Time courses of leukocytes in arm 2 showed more severe but not more prolonged leukocytopenia compared with arm 1. WHO grades 3-4 infections were documented in 2.1% (arm 1) and 3.1% (arm 2) of all cycles. Erythrocytes were transfused in 6% (arm 1) and 28% (arm 2), platelets in < 1% (arm 1) and 6% (arm 2) of all cycles.Conclusions: Both BEACOPP schemes are practicable in a large multicenter setting. Despite increased hematotoxicity, moderate dose escalation is safe for the majority of the patients with G-CSF assistance and standard supportive treatment.