TY - JOUR
T1 - Oxaliplatin-mediated increase in spleen size as a biomarker for the development of hepatic sinusoidal injury
AU - Overman, Michael J.
AU - Maru, Dipen M.
AU - Charnsangavej, Chusilp
AU - Loyer, Evelyn M.
AU - Wang, Huamin
AU - Pathak, Priyanka
AU - Eng, Cathy
AU - Hoff, Paulo M.
AU - Vauthey, Jean Nicolas
AU - Wolff, Robert A.
AU - Kopetz, Scott
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2010/5/20
Y1 - 2010/5/20
N2 - Purpose: 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. Patients and Methods: 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. Results: Spleen size increased in 86% of patients treated with adjuvant FOLFOX (P < .001), with a ≥ 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 ≥ 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. Conclusion: 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.
AB - Purpose: 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. Patients and Methods: 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. Results: Spleen size increased in 86% of patients treated with adjuvant FOLFOX (P < .001), with a ≥ 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 ≥ 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. Conclusion: 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.
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U2 - 10.1200/JCO.2009.27.5701
DO - 10.1200/JCO.2009.27.5701
M3 - Article
C2 - 20406923
AN - SCOPUS:77956399254
SN - 0732-183X
VL - 28
SP - 2549
EP - 2555
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 15
ER -