Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Thoracic Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
J Natl Cancer Inst. 2018 Aug 1;110(8):888-894. doi: 10.1093/jnci/djx288.
Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI), portal hypertension, and splenic sequestration of platelets. Evidence suggests that bevacizumab may protect against HSI.
Two cohorts of metastatic colorectal cancer (CRC) were analyzed: a nonrandomized exploratory cohort of 184 patients treated at a single institution from 2003 to 2010 and a confirmatory cohort of 200 patients from a multi-institutional randomized trial (NO16966). All patients were treated with frontline fluoropyrimidine and oxaliplatin with or without bevacizumab. Changes in splenic volumes and platelet counts were compared by treatment, two-sided log-rank test.
In the exploratory cohort, the bevacizumab-treated patients (n = 138) compared with the nonbevacizumab-treated patients (n = 46) demonstrated a longer median time to splenic enlargement (≥30%, P = .02) and reduced rate of thrombocytopenia (<150 000/mm3, P = .04). In the confirmatory cohort (106 bevacizumab arm and 94 placebo arm), the median time to a spleen enlargement of 30% or more was 7.6 vs 5.4 (P = .01), and six-month cumulative incidence of thrombocytopenia (platelets < 100 000/mm3) was 19% vs 51% (P < .001) for bevacizumab compared with placebo. The development of an increasing spleen size was associated with the risk of either grade 1 or grade 2 thrombocytopenia (P < .001). The cumulative rate of grade 1 or grade 2 thrombocytopenia was statistically less in the bevacizumab arm, with six-month grade 2 thrombocytopenia rates of 4% vs 23% (P < .001). Patients with a large spleen prior to chemotherapy initiation appeared to be at highest risk of this toxicity.
In metastatic CRC, the addition of bevacizumab to oxaliplatin-based chemotherapy reduces the frequency of splenic enlargement and the rate of thrombocytopenia.
奥沙利铂为基础的化疗可导致肝窦状隙损伤（HSI）、门静脉高压和脾脏血小板隔离。有证据表明贝伐单抗可能对 HSI 有保护作用。
分析了两组转移性结直肠癌（CRC）患者：2003 年至 2010 年在一家机构治疗的 184 例非随机探索性队列和来自多机构随机试验（NO16966）的 200 例验证性队列。所有患者均接受一线氟嘧啶和奥沙利铂联合或不联合贝伐单抗治疗。采用双侧对数秩检验比较两组治疗前后脾脏体积和血小板计数的变化。
在探索性队列中，贝伐单抗治疗组（n=138）与非贝伐单抗治疗组（n=46）相比，脾脏增大（≥30%）的中位时间更长（P=0.02），血小板减少（<150000/mm3）的发生率更低（P=0.04）。在验证性队列（106 例贝伐单抗组和 94 例安慰剂组）中，脾脏增大 30%或更多的中位时间为 7.6 与 5.4（P=0.01），贝伐单抗组 6 个月时血小板减少（血小板<100000/mm3）的累积发生率为 19%，而安慰剂组为 51%（P<0.001）。脾脏增大的发生与 1 级或 2 级血小板减少的风险相关（P<0.001）。贝伐单抗组的 1 级或 2 级血小板减少发生率明显较低，6 个月时 2 级血小板减少发生率为 4%与 23%（P<0.001）。化疗前脾脏较大的患者似乎发生这种毒性的风险最高。
在转移性 CRC 中，奥沙利铂为基础的化疗联合贝伐单抗可降低脾脏增大和血小板减少的频率。
