Fields K K, Elfenbein G J, Perkins J B, Janssen W E, Ballester O F, Hiemenz J W, Zorsky P E, Kronish L E, Foody M C
Department of Internal Medicine, University of South Florida, Tampa.
Semin Oncol. 1994 Oct;21(5 Suppl 12):86-92.
We treated 115 patients in a phase I/II dose-escalation study of ifosfamide/carboplatin/etoposide (ICE) followed by autologous stem cell rescue. Patients treated had a variety of diagnoses, including breast cancer (high-risk stage II disease with eight or more positive nodes, stage III disease, and responsive metastatic disease), non-Hodgkin's lymphoma, Hodgkin's disease, acute leukemia in first remission, and various solid tumors that were responsive to induction therapy. Patients received autologous bone marrow stem cells or peripheral blood stem cells primed by one of several methods. The maximum tolerated dose of ICE was determined to be ifosfamide 20,100 mg/m2, carboplatin 1,800 mg/m2, and etoposide 3,000 mg/m2 when administered as a 6-day regimen. The dose-limiting toxicities included acute renal failure, severe central nervous system toxicity, and "leaky capillary syndrome" with hypoalbuminemia, profound fluid overload, and pulmonary insufficiency. Analysis of hematologic recovery based on stem cell source and influence of hematopoietic growth factor administration was undertaken. Hematopoietic growth factor use significantly reduced neutrophil engraftment time for patients receiving bone marrow stem cells, with evidence of earlier recovery times for patients receiving granulocyte colony-stimulating factor compared with granulocyte-macrophage colony-stimulating factor. Neutrophil recovery times varied based on the source of stem cells used, with the earliest engraftment times seen for patients receiving peripheral blood stem cells primed with cyclophosphamide and granulocyte colony-stimulating factor. Platelet recovery times were not statistically different for any of the subsets. In conclusion, the maximum tolerated dose of ICE has been defined, and the source of stem cells and the use of hematopoietic growth factors influence hematopoietic recovery.
我们在一项异环磷酰胺/卡铂/依托泊苷（ICE）的I/II期剂量递增研究中对115例患者进行了治疗，随后进行自体干细胞救援。接受治疗的患者有多种诊断，包括乳腺癌（高危II期疾病，有八个或更多阳性淋巴结、III期疾病和反应性转移性疾病）、非霍奇金淋巴瘤、霍奇金病、首次缓解期的急性白血病以及对诱导治疗有反应的各种实体瘤。患者接受了通过几种方法之一预处理的自体骨髓干细胞或外周血干细胞。当作为6天疗程给药时，ICE的最大耐受剂量确定为异环磷酰胺20,100mg/m²、卡铂1,800mg/m²和依托泊苷3,000mg/m²。剂量限制性毒性包括急性肾衰竭、严重的中枢神经系统毒性以及伴有低白蛋白血症、严重液体超负荷和肺功能不全的“毛细血管渗漏综合征”。对基于干细胞来源的血液学恢复以及造血生长因子给药的影响进行了分析。造血生长因子的使用显著缩短了接受骨髓干细胞患者的中性粒细胞植入时间，与接受粒细胞-巨噬细胞集落刺激因子的患者相比，接受粒细胞集落刺激因子的患者有更早恢复时间的证据。中性粒细胞恢复时间因所用干细胞来源而异，接受环磷酰胺和粒细胞集落刺激因子预处理的外周血干细胞的患者植入时间最早。任何亚组的血小板恢复时间在统计学上均无差异。总之，已确定了ICE的最大耐受剂量，干细胞来源和造血生长因子的使用会影响造血恢复。
