Chen Amy, Chen Li, Al-Qaisi Abeer, Romond Edward, Awasthi Mukta, Kadamyan-Melkumyan Vera, Massarweh Suleiman
University of Kentucky, Lexington, KY.
University of Kentucky, Lexington, KY; Markey Cancer Center, Lexington, KY.
Clin Breast Cancer. 2015 Feb;15(1):48-53. doi: 10.1016/j.clbc.2014.07.002. Epub 2014 Aug 15.
Everolimus, which inhibits the mammalian target of rapamycin (mTOR), is increasingly used in breast cancer and familiarity with its full range of toxicity is critical for practicing oncologists.
We studied hematologic changes in 31 patients with metastatic breast cancer treated in a phase II clinical trial using everolimus. Complete blood counts were collected at baseline, 2 weeks, 4 weeks, every 4 weeks during treatment, and 1 month after discontinuation. Adverse events were defined using Common Toxicity Criteria version 3. Linear mixed models with fixed effects of time and random intercepts and slopes were used to study trends and comparisons were conducted using paired t tests.
Anemia was reported in 22 patients (71%), thrombocytopenia in 17 (55%), and leukopenia in 14 (45%). These were predominantly grade 1 or 2 and did not require dose modification. Red blood cell mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) both decreased significantly over time (P < .0001) starting at 2 weeks with no significant change in mean corpuscular hemoglobin concentration (MCHC) (P = .104). Both MCV and MCH increased 1 month after treatment discontinuation (P values < .0001 and .0003, respectively) indicating reversibility of this effect. Although total leukocyte counts remained largely stable, lymphocyte percentage progressively decreased over time with a trend for increased neutrophils.
In addition to anemia, leukopenia, and thrombocytopenia, everolimus consistently induces red cell microcytosis and reduced hemoglobin content. Lymphopenia may contribute to immune suppression and increased risk of infection. Familiarity with these hematologic changes is prudent as more patients are treated with this class of drugs.
依维莫司可抑制哺乳动物雷帕霉素靶蛋白（mTOR），在乳腺癌治疗中的应用日益广泛，对于肿瘤专科医生而言，全面了解其毒性至关重要。
我们对31例转移性乳腺癌患者进行了一项II期临床试验，使用依维莫司治疗，研究血液学变化。在基线、2周、4周、治疗期间每4周以及停药后1个月采集全血细胞计数。使用3版常见毒性标准定义不良事件。采用具有时间固定效应以及随机截距和斜率的线性混合模型研究趋势，并使用配对t检验进行比较。
22例患者（71%）报告有贫血，17例（55%）有血小板减少，14例（45%）有白细胞减少。这些主要为1级或2级，无需调整剂量。红细胞平均体积（MCV）和平均血红蛋白含量（MCH）自2周起均随时间显著下降（P <.0001），而平均血红蛋白浓度（MCHC）无显著变化（P = 0.104）。停药1个月后，MCV和MCH均升高（P值分别<.0001和.0003），表明这种效应具有可逆性。尽管总白细胞计数基本保持稳定，但淋巴细胞百分比随时间逐渐下降，中性粒细胞有增加趋势。
除贫血、白细胞减少和血小板减少外，依维莫司持续诱导红细胞小红细胞症和血红蛋白含量降低。淋巴细胞减少可能导致免疫抑制并增加感染风险。鉴于越来越多的患者使用这类药物，了解这些血液学变化是明智的。
