GSTM1-Null Genotype Predicts Oxaliplatin-Associated Sinusoidal Obstruction Syndrome in Metastatic Colorectal Cancer

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(ChemotherapyAdvisor) – In patients receiving neoadjuvant oxaliplatin for metastatic colorectal cancer (mCRC), glutathione S-transferase (GST) M1 (GSTM1)-null genotype is associated with an elevated risk of moderate to severe sinusoidal obstruction syndrome (SOS), a frequent complication of oxaliplatin therapy, report authors of a study published in the British Journal of Cancer.

“The GSTM1-null genotype is an independent risk factor for SOS,” wrote lead author Celien PH Vreuls, MD, of the Department of Pathology, Maastricht University Medical Center, the Netherlands, and coauthors. “This finding allows us, in association with other risk factors, to conceive a potential risk profile predicting whether the patient is at risk of developing SOS, before starting oxaliplatin, and subsequently might result in adjustment of treatment.”

SOS is associated with decreased overall survival rates, the authors noted. Predicting which patients are likely to suffer this side-effect when administered oxaliplatin would help tailor treatments to individual patients and might help to improve mCRC survival times.

Histopathologic study of non–tumor-bearing liver genotypes was performed with polymerase chain reaction for 55 patients, 32 (58%) of whom had SOS lesions (22% of the SOS lesions were moderate and 9% were severe). GSTM1-null genotype significantly correlated with SOS (P=0.013), the authors reported. In a multivariate model that included other prognostic factors, GSTM1-null genotype remained significantly associated with moderate or severe SOS (P=0.026), the authors reported. Other prognostic factors included in the statistical model, including GSTT1 genotypes, oxaliplatin cumulative dose, and administration of additional bevacizumab, did not correlate significantly with the risk of moderate or severe SOS in this analysis, the authors reported.

Additional bevacizumab was administered to 69% of the study participants, which can reduce the risk of SOS but was equally represented among the study's GSTM1-positive and –negative genotype patients, they noted. “As these patients are equally divided among both groups (GSTM1-null and GSTM1-positive) it is less likely that this drug would influence our results,” they noted. “However, a more ideal comparison would consist of patients solely treated with oxaliplatin.”

Abstract 

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