Impact of CAPOX or FOLFOX4 on Spleen Size, Platelet Count and Liver Function when Partnered Cetuximab As First-line Treatment for KRAS Wild-type Metastatic Colorectal Cancer

Objectives: Oxaliplatin can cause hepatic sinusoidal injury and splenomegaly. It remains unknown if the magnitude of injury would differ when oxaliplatin is combined with capecitabine or 5-FU with/without cetuximab. We investigated the impact of 1 st line CAPOX or FOLFOX4 and the additional cetuximab on spleen size, platelet count and liver function in patients with KRAS wild-type metastatic colorectal cancer (mCRC). Methods: 101 Patients planned to receive either CAPOX or FOLFOX4 with/without cetuximab as first-line treatment were prospectively recruited. Changes in spleen size by volumetric measurement after treatment were determined. Correlation studies were performed for factors associated with changes in spleen size, thrombocytopenia and impaired liver function. Results: The spleen enlarged (median +17.9%, P < 0.001) after treatment. Multivariable analysis revealed that capecitabine, its dose intensity and cumulative dose (per 10000mg increase) correlated with splenomegaly (P = 0.01, P = 0.02 and P = 0.006, respectively). Increase in spleen size (P = 0.004) and splenomegaly (P = 0.002) correlated with thrombocytopenia. Dose intensity and cumulative dose of capecitabine (per 10000mg increase) and increase in spleen size correlated with grade 1 impaired liver function (P = 0.01, P = 0.003 and P = 0.04, respectively). Use of cetuximab correlated with less splenic enlargement (+13.7% vs. +22.7%; P = 0.04), especially when coupled with FOLFOX4 rather than CAPOX (+1.1% vs. + 23.0%; P = 0.003). Conclusions: Capecitabine was associated with more splenomegaly which in turn correlated with thrombocytopenia and impaired liver function. Cetuximab offered some protection from further splenic enlargement especially when combined with FOLFOX4.