Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
J Clin Oncol. 2010 May 20;28(15):2549-55. doi: 10.1200/JCO.2009.27.5701. Epub 2010 Apr 20.
Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury, with resultant sinusoidal damage and portal hypertension. We sought to explore the relationship between oxaliplatin induced hepatic sinusoidal injury, increases in spleen size, and the subsequent development of thrombocytopenia.
We retrospectively assessed the relationship between chemotherapy exposure, changes in spleen size (determined by volumetric measurements), and platelet counts in 136 patients treated with adjuvant fluorouracil and oxaliplatin (FOLFOX) or fluoropyrimidine for stage II or III colorectal adenocarcinoma. Hepatic sinusoidal injury and changes in spleen size were graded in a separate population of 63 patients with metastatic colorectal cancer receiving fluoropyrimidine and oxaliplatin before liver resection.
Spleen size increased in 86% of patients treated with adjuvant FOLFOX (P < .001), with a > or = 50% increase in 24% of patients. Spleen size did not significantly increase in patients treated with adjuvant fluoropyrimidine. Increases in spleen size correlated with cumulative oxaliplatin dose (P = .003). Patients with splenic enlargement > or = 50% had higher rates of thrombocytopenia in the first year after completion of chemotherapy (27% v 5%; P = .003). In patients with hepatic metastases treated with preoperative fluoropyrimidine and oxaliplatin, increases in spleen size was a predictor of higher histologic grades of sinusoidal injury in both univariate (P = .03) and multivariate (P = .02) analyses.
Increases in spleen size correlate with increasing grade of hepatic sinusoidal injury and can serve as a simple method for identifying patients at risk for this toxicity. Oxaliplatin-induced increases in spleen size should be recognized as a potential etiology of persistent thrombocytopenia after oxaliplatin treatment.
奥沙利铂为基础的化疗可导致肝窦损伤，继而引发窦状隙损伤和门脉高压。我们旨在探索奥沙利铂诱导的肝窦损伤、脾脏增大与随后发生血小板减少症之间的关系。
我们回顾性评估了 136 例接受氟尿嘧啶和奥沙利铂（FOLFOX）或氟嘧啶辅助治疗 II 期或 III 期结直肠腺癌患者的化疗暴露、脾脏大小变化（通过体积测量确定）与血小板计数之间的关系。在另一组 63 例接受氟嘧啶和奥沙利铂治疗的转移性结直肠癌患者中，在肝切除术前评估了肝窦损伤和脾脏大小变化。
接受辅助 FOLFOX 治疗的患者中 86%的脾脏增大（P＜0.001），其中 24%的患者脾脏增大＞或=50%。接受辅助氟嘧啶治疗的患者脾脏大小无明显增加。脾脏增大与奥沙利铂累积剂量相关（P=0.003）。化疗完成后第一年，脾脏增大＞或=50%的患者血小板减少症发生率更高（27%比 5%；P=0.003）。在接受术前氟嘧啶和奥沙利铂治疗的肝转移患者中，脾脏增大是肝窦损伤组织学分级较高的单因素（P=0.03）和多因素（P=0.02）分析的预测因素。
脾脏增大与肝窦损伤程度增加相关，可作为识别此类毒性风险患者的一种简单方法。奥沙利铂诱导的脾脏增大应被视为奥沙利铂治疗后持续性血小板减少症的潜在病因。
