Risk Factors of MFOLFOX6-induced Hyperammonemia in Patients with Colorectal Cancer: an Observational Study

Background: FOLFOX therapy, a standard treatment for colorectal cancer (CRC), causes a rare, but serious adverse event, hyperammonemia. However, the risk factors of hyperammonemia remain unknown.

Methods: We examined 74 patients who received mFOLFOX6 therapy with or without biologics for CRC between April 2013 and March 2018 in Yaizu City Hospital. Clinicopathological factors were retrospectively reviewed in association with hyperammonemia, and risk factors of hyperammonemia during mFOLFOX6 therapy were analyzed in 32 patients with the available data.

Results: Seven patients developed hyperammonemia, with onset exclusively on day 2 or 3 in the first cycle of therapy. They were treated with branched chain amino acid administration and hydration; however, one patient with stage G4 chronic kidney disease (CKD) died. By multivariate analysis, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m was independently associated with hyperammonemia during FOLFOX therapy (odds ratio: 9.0, p = 0.040).

Conclusions: Reduced eGFR is considered a risk factor of developing hyperammonemia during FOLFOX therapy. Serum ammonia levels should be monitored especially during the first cycle of FOLFOX therapy in patients with CKD stage G3 or higher.