Investigation of the efficacy of reduced coenzyme Q10 (CoQ10) for alleviating acute intestinal toxicity associated with pelvic radiotherapy: A randomized, placebo-controlled, double-blind comparative study

Background: Diarrhea is one of the major acute adverse effects in patients undergoing pelvic radiotherapy, often impairing treatment continuity and quality of life. Despite its clinical importance, the pathogenesis of radiation-induced diarrhea (RID) remains inadequately understood, and effective prophylactic strategies have yet to be established. Reduced coenzyme Q10 (rCoQ10) possesses antioxidant properties capable of neutralizing activated reactive oxygen species generated during irradiation. This study aimed to evaluate whether oral administration of rCoQ10 could mitigate intestinal mucosal damage and reduce the severity of diarrhea in patients receiving curative pelvic radiotherapy. Materials and Methods: This randomized, placebo-controlled clinical study included patients with cervical, endometrial, or vaginal cancer (FIGO 2018 Stage IB-IVA) treated with radiotherapy at Kobe University Hospital between June 2021 and November 2023. Eligible patients were ≥20 years old, had ECOG Performance Status 0-2, and provided written informed consent. A total of 47 patients were randomized into rCoQ10 and placebo groups. Participants received three 200 mg soft capsules of rCoQ10 or placebo orally once daily starting 5-7 days before radiotherapy. From the first day of radiotherapy, capsules were taken once daily approximately one hour before each irradiation session. Thirty patients (63.8%) underwent IMRT, and 33 patients (70.2%) received concurrent chemotherapy with weekly cisplatin (40 mg/m²). Adverse events, including diarrhea, were graded according to CTCAE version 5.0. The primary endpoint was the maximum increase in the number of daily bowel movements during the radiotherapy period. Analyses were adjusted for chemotherapy use and radiotherapy modality. Results: Among the 47 enrolled patients, 44 were evaluable for analysis (two withdrew consent and one discontinued due to cognitive decline). The median maximum increase in bowel movements was 5.3 in the rCoQ10 group and 5.8 in the placebo group, showing no significant difference (p = 0.937). While the overall incidence and severity distribution of diarrhea did not significantly differ, a trend toward reduced occurrence of Grade 2 diarrhea was observed in the rCoQ10 group. The 2-year progression-free survival was 80.4% in the rCoQ10 group and 84.0% in the placebo group (p = 0.491), indicating no negative influence on oncologic treatment efficacy. No serious adverse events related to rCoQ10 were reported. Conclusions: Although the primary endpoint was not met, rCoQ10 showed a potential benefit in reducing moderate diarrhea in patients undergoing pelvic radiotherapy, without compromising cancer treatment outcomes. Further large-scale studies are warranted to clarify its clinical utility as a supportive therapy.