The Role of Lovastatin in Curative Chemoradiotherapy for Patients with Head and Neck Cancer: A Randomized Trial

Background: Evidence suggests that statins can improve survival outcomes and ameliorate treatment-related side-effects in certain malignancies. Statins exhibit various mechanisms of action, including apoptosis induction, proliferation inhibition, tumor radiosensitization, lipid production suppression, and anti-inflammatory effects. This trial aimed to assess the impact of lovastatin on patients with locally advanced head and neck squamous cell carcinoma (HNSCC) undergoing definitive chemoradiation.Method: In this double-blinded randomized phase ۲ clinical trial, ۳۵ patients were randomly allocated to receive either ۸۰ mg of lovastatin daily in conjunction with chemoradiotherapy (case group, n=۱۸) or a placebo (control group). Primary outcomes included the response rate (RR) after three months, the occurrence of acute/late side-effects, median progression-free survival (PFS), and overall survival (OS).Results: The complete RR was slightly higher in the statin group (۸۳.۳% vs. ۶۴.۷%), although it did not reach statistical significance (P = ۰.۵۹۲). Acute adverse events did not significantly differ between the two groups. Grade ۳ dermatitis occurred more frequently in the placebo group (۳۵.۳% vs. ۱۱.۱%), while grade ۳ mucositis was more common in the statin group (۳۸.۹% vs. ۱۱.۸%). The median OS was ۲۲ months (confidence interval (CI) ۹۵% = ۶.۳-۳۷.۶) in the statin group and ۱۷ months (CI ۹۵% = ۴.۹-۲۹.۱) in the control group (P = ۰.۵۰). Median PFS was ۲۰ months (CI ۹۵% = ۱۵.۸-۲۴.۱) in the statin group and ۱۵ months (CI ۹۵% = ۸.۲-۲۱.۷) in the control group (P = ۰.۶۰۹).Conclusion: Combining lovastatin with chemoradiation augments the therapeutic effect in HNSCC. Larger-scale studies incorporating advanced radiotherapy techniques and baseline lipid profile assessments are necessary to investigate statins' efficacy in HNSCC further.