Winer Eric S, Safran Howard, Karaszewska Boguslawa, Bauer Sebastian, Khan Dilawar, Doerfel Steffen, Burgess Paul, Kalambakas Stacey, Mostafa Kamel Yasser, Forget Frederic
Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
Brown University Oncology Research Group, Providence, RI, USA.
Int J Hematol. 2017 Dec;106(6):765-776. doi: 10.1007/s12185-017-2319-9. Epub 2017 Sep 1.
In this phase 2 study, patients with solid tumors receiving gemcitabine monotherapy or gemcitabine plus cisplatin/carboplatin were randomized 2:1 to eltrombopag 100 mg (n = 52) or placebo (n = 23) for 5 days before and after chemotherapy was started. The primary endpoint was prechemotherapy (Day 1) platelet count across ≤6 cycles. Prechemotherapy platelet counts were numerically higher with eltrombopag than placebo. Frequencies of grades 3/4 thrombocytopenia were lower with eltrombopag in both the combination therapy (77 vs. 100%) and monotherapy (36 vs. 42%) groups. Proportionately fewer eltrombopag-treated patients had platelet counts <100 × 10/L at nadir. Among patients receiving combination chemotherapy, mean time to recovery from platelet nadir was 8 days with eltrombopag vs. 15 days with placebo. Eltrombopag-treated patients had fewer dose delays/reductions or missed doses due to thrombocytopenia in both the combination therapy (77 vs. 91%) and monotherapy (62 vs. 83%) groups. Adverse events and serious adverse events were less frequent with eltrombopag in both chemotherapy groups, with reduced rates of anemia, neutropenia, and thrombocytopenia in patients receiving combination chemotherapy. In conclusion, eltrombopag treatment shortened the time to recovery from platelet nadir in patients treated with gemcitabine-based chemotherapy and reduced dose delays/reductions due to thrombocytopenia.
在这项2期研究中，接受吉西他滨单药治疗或吉西他滨联合顺铂/卡铂治疗的实体瘤患者，在化疗开始前和开始后5天，按2:1随机分组接受艾曲泊帕100 mg（n = 52）或安慰剂（n = 23）治疗。主要终点是≤6个周期化疗前（第1天）的血小板计数。化疗前，艾曲泊帕组的血小板计数在数值上高于安慰剂组。在联合治疗组（77%对100%）和单药治疗组（36%对42%）中，艾曲泊帕治疗的3/4级血小板减少症发生率均较低。在最低点时，接受艾曲泊帕治疗的患者血小板计数<100×10⁹/L的比例相对较少。在接受联合化疗的患者中，艾曲泊帕治疗组从血小板最低点恢复的平均时间为8天，而安慰剂组为15天。在联合治疗组（77%对91%）和单药治疗组（62%对83%）中，接受艾曲泊帕治疗的患者因血小板减少导致的剂量延迟/减少或漏服剂量较少。在两个化疗组中，艾曲泊帕治疗的不良事件和严重不良事件发生率均较低，接受联合化疗的患者贫血、中性粒细胞减少和血小板减少的发生率降低。总之，艾曲泊帕治疗缩短了接受基于吉西他滨化疗患者从血小板最低点恢复的时间，并减少了因血小板减少导致的剂量延迟/减少。
