Biocurcumin as Radiosensitiser for Cervical Cancer Study (BRACES): A Double-Blind Randomised Placebo-Controlled Trial

Abstract

Cervical cancer is a leading cause of death among women worldwide, particularly in Indonesia. The main treatment of advanced-stage cervical cancer is radiation; however, the outcomes do not meet the required expectations. [1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5dione] has been reported in several studies for its potency in cancer therapy. This study aims to investigate the clinical and molecular [(malondialdehyde (MDA) and NF-κB levels] effects, apoptotic index, and safety of Biocurcumin (BCM-95) as a radiosensitiser in cervical cancer. In this double-blind placebo randomised-controlled trial, we randomised 121 patients into 2 groups (BCM-95 or placebo). MDA and their NF-κB levels and apoptotic index were measured before and after administering 24 Gy of radiation. MDA was identified using Wills’ method, whereas NF-κB was identified via ELISA. The apoptotic index was identified using TUNEL and DAPI staining. The clinical response was classified based on the RECIST. MDA levels before radiation were similar between both groups in per protocol and intention-to-treat (ITT) analyses (p=0.53 and p=0.16, respectively). After radiation, MDA levels increased in both groups with no significant differences in per protocol and ITT analyses (p=0.52 and p=0.18, respectively). NF-κB levels before radiation were similar between the two groups in per protocol and ITT analyses (p=0.92 and p=0.98, respectively). After radiation, the BCM-95 group showed an increase in the NF-κB levels compared with the placebo group in per protocol analysis but not in ITT analysis (p=0.018 and p=0.42, respectively). The BCM-95 group had a higher apoptotic index before radiation in per protocol analysis but not in ITT analysis (p=0.01 and p=0.61, respectively). After radiation, the apoptotic index remained higher in the BCM-95 group in per protocol analysis but not in ITT analysis (p=0.04 and p=0.91, respectively). There was no significant difference in complete response between the groups (per protocol, p=0.61; ITT analysis, p=0.90). Although BCM-95 can regulate ROS, NF-κB, and apoptosis in human cervical cancer, it is not significant. Therefore, BCM-95 does not improve clinical response to radiation treatment.