Change Rate in Serum Nitric Oxide May Affect Lenvatinib Therapy in Hepatocellular Carcinoma

Background: Lenvatinib is appropriate for reducing the production of nitric oxide (NO) and facilitating as block angiogenesis. However, to our knowledge, there are no data that support the correlation between NO and clinical response in patients who received lenvatinib therapy for HCC. Therefore, we investigated whether or not NO influence a therapeutic response and adverse events (AEs) after lenvatinib therapy for unresectable hepatocellular carcinoma (HCC). Methods: This study was conducted using previously collected data from another study. We enrolled 70 patients who received lenvatinib for advanced or unresectable HCC. NO was measured by converting nitrate (NO 3 – ) to nitrite (NO 2 – ) with nitrate reductase, followed by quantitation of NO 2 – based on Griess reagent. To determine whether lenvatinib influences NO in unresectable HCC, we evaluated the influence of maximal therapeutic response and SAE on the change rate of NO from baseline after administration of lenvatinib. Results: : After lenvatinib administration, a change rate in the NO from 0.27 to 4.16 was observed. There was no difference between the clinical response to lenvatinib and the change rate of NO (P = 0.193). However, the change rate of NO was significantly higher in patients with AEs than in those without AEs (P = 0.013). When a reduction in NO rate of < 0.8 was defined as a clinically significant reduction of NO (CSRN), the CSRN group had significantly worse progression-free survival (PFS) and overall survival (OS) than the non-CSRN group (P = 0.040 and P = 0.005, respectively) Conclusion: Decreased NO levels were associated with the occurrence of AEs and worse prognosis after lenvatinib administration. Change rate in serum NO can be used as predictive markers in patients receiving lenvatinib therapy for HCC.