Oxaliplatin-mediated increase in spleen size as a biomarker for the development of hepatic sinusoidal injury.
OBJECTIVE
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.


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 > 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.


CONCLUSIONS
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.
Overman
Michael J
MJ
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. moverman@mdanderson.org
Maru
Dipen M
DM
Charnsangavej
Chusilp
C
Loyer
Evelyn M
EM
Wang
Huamin
H
Pathak
Priyanka
P
Eng
Cathy
C
Hoff
Paulo M
PM
Vauthey
Jean-Nicolas
JN
Wolff
Robert A
RA
Kopetz
Scott
S
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D000077150:Oxaliplatin; D010976:Platelet Count; D011379:Prognosis; D012004:Rectal Neoplasms / Q000097:blood / Q000188:drug therapy; D012189:Retrospective Studies; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013163:Splenomegaly / Q000139:chemically induced*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin