Gianni A M, Bregni M, Siena S, Magni M, Di Nicola M, Lombardi F, Tarella C, Pileri A, Bonadonna G
Cristina Gandini Bone Marrow Transplantation Unit, Istituto Nazionale Tumori, Milan, Italy.
J Clin Oncol. 1992 Dec;10(12):1955-62. doi: 10.1200/JCO.1992.10.12.1955.
This study assessed the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or recombinant human granulocyte colony-stimulating factor (rhG-CSF) in ameliorating the extent and duration of hematologic toxicity after high-dose etoposide cancer therapy.
Thirty-two non-Hodgkin's lymphoma and myeloma patients were treated with 2 to 2.4 g/m2 etoposide infused intravenously (IV) during a 10- to 12-hour period, followed 72 hours later by subcutaneous administration of rhGM-CSF or rhG-CSF. Hematologic toxicity was compared with that observed in 29 patients who were treated with high-dose etoposide without growth factors.
The median duration of grade 4 neutropenia in growth factor-treated patients was 3 days, and granulocyte counts never decreased to less than 100/microL in approximately half of the patients. The corresponding figures in the control patients were 8 and 3 days, respectively (P < .0001). No effect was observed in platelet and RBC recovery. Growth factor-treated patients became eligible to receive additional myelotoxic chemotherapy a median of 5 days earlier than controls. Nonhematologic toxicity was minimal. Grade 1 mucositis was observed in two of 61 patients (3%). Antitumor activity assessed within 1 month after etoposide administration was documented in 58% of 38 assessable patients. Finally, high-dose etoposide expanded and mobilized the pool of peripheral-blood hematopoietic progenitors.
The use of rhGM-CSF or rhG-CSF makes high-dose etoposide a safe outpatient regimen and should encourage the inclusion of this highly effective and well-tolerated drug in novel treatment strategies that use high-dose therapy early in the clinical course of chemosensitive tumors.
本研究评估重组人粒细胞巨噬细胞集落刺激因子(rhGM-CSF)或重组人粒细胞集落刺激因子(rhG-CSF)改善高剂量依托泊苷癌症治疗后血液学毒性的程度和持续时间的疗效。
32例非霍奇金淋巴瘤和骨髓瘤患者在10至12小时内静脉输注2至2.4 g/m²依托泊苷,72小时后皮下给予rhGM-CSF或rhG-CSF。将血液学毒性与29例接受高剂量依托泊苷但未使用生长因子治疗的患者进行比较。
接受生长因子治疗的患者4级中性粒细胞减少的中位持续时间为3天,约一半患者的粒细胞计数从未降至低于100/μL。对照患者的相应数字分别为8天和3天(P <.0001)。在血小板和红细胞恢复方面未观察到效果。接受生长因子治疗的患者比对照组中位提前5天有资格接受额外的骨髓毒性化疗。非血液学毒性最小。在接受治疗的61例患者中有2例(3%)出现1级黏膜炎。在38例可评估患者中,58%在依托泊苷给药后1个月内记录到抗肿瘤活性。最后,高剂量依托泊苷扩大并动员了外周血造血祖细胞库。
rhGM-CSF或rhG-CSF的使用使高剂量依托泊苷成为一种安全的门诊治疗方案,并应鼓励将这种高效且耐受性良好的药物纳入在化疗敏感肿瘤临床病程早期使用高剂量治疗的新型治疗策略中。