Shea Thomas C, Beaven Anne W, Moore Dominic T, Serody Jonathan S, Gabriel Don A, Chao Nelson, Gockerman Jon P, Garcia Reynaldo A, Rizzieri David A
Division of Hematology/Oncology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Leuk Lymphoma. 2009 May;50(5):741-8. doi: 10.1080/10428190902853136.
Non-cross resistant drugs given at high-dose intensity may maximise tumor cell kill leading to improved patient outcomes. We investigated the feasibility and efficacy of administering ifosfamide, carboplatin and etoposide +/- rituximab as sequential high-dose single agents. Twenty-two patients with relapsed/refractory Hodgkin lymphoma (n = 9) or non-Hodgkin (n = 13) lymphoma (NHL) were included. Therapy included: cycle 1 ifosfamide (15 g/m(2)), cycle 2 etoposide (900 mg/m(2)) and cycle 3 carboplatin (area under the curve 15). Patients with NHL received rituximab (375 mg/m(2)) with cycles 1 and 2. Blood stem cell collection was performed after etoposide. Primary endpoints were overall response (complete response (CR) + PR) and ability to mobilise stem cells after etoposide. Secondary endpoints were to assess the toxicity of the regimen and to evaluate the ability of patients to proceed to stem cell transplant (SCT). Overall response rate was 54% with CR in 4/22 (18%) subjects and PR in 8/22 (36%). Median progression-free survival was 15 months and overall survival has not been reached at 40 months. Thirteen participants proceeded to SCT. Grade 3/4 thrombocytopenia and neutropenia occurred in 58% of cycles and 91% of subjects respectively. Forty-five percent of patients required hospitalisation for toxicity and two patients died from complications of therapy. Sequential dose intense ifosfamide, etoposide, carboplatin +/- rituximab was more toxic and no more effective than the same drugs given in a conventional fashion.
给予高剂量强度的非交叉耐药药物可能会使肿瘤细胞杀伤最大化，从而改善患者预后。我们研究了序贯给予高剂量单药异环磷酰胺、卡铂和依托泊苷±利妥昔单抗的可行性和疗效。纳入了22例复发/难治性霍奇金淋巴瘤患者（n = 9）或非霍奇金淋巴瘤（n = 13）（NHL）患者。治疗方案包括：第1周期给予异环磷酰胺（15 g/m²），第2周期给予依托泊苷（900 mg/m²），第3周期给予卡铂（曲线下面积为15）。NHL患者在第1和第2周期接受利妥昔单抗（375 mg/m²）。在给予依托泊苷后进行造血干细胞采集。主要终点是总体缓解率（完全缓解（CR）+部分缓解（PR））以及给予依托泊苷后动员干细胞的能力。次要终点是评估该方案的毒性以及评估患者进行干细胞移植（SCT）的能力。总体缓解率为54%，4/22（18%）的受试者达到CR，8/22（36%）的受试者达到PR。无进展生存期的中位数为15个月，40个月时总生存期尚未达到。13名参与者进行了SCT。3/4级血小板减少症和中性粒细胞减少症分别发生在58%的周期和91%的受试者中。45%的患者因毒性反应需要住院治疗，2例患者死于治疗并发症。序贯给予高剂量强度的异环磷酰胺、依托泊苷、卡铂±利妥昔单抗比以传统方式给予相同药物毒性更大且疗效并不更佳。
