This article summarizes a case report published in Frontiers in Medicine describing the treatment of a 79-year-old man with treatment-refractory metastatic castration-resistant prostate cancer (mCRPC). The patient had progressed on all standard therapies, including 177Lu-PSMA radioligand therapy (PRLT) and TANDEM-PRLT, which combines 177Lu-PSMA and 225Ac-PSMA.
The patient was treated with 177Lu-PRLT combined with benfo-oxythiamine (B-OT), a novel thiamine analog that inhibits transketolase enzymes. Transketolase enzymes are essential for DNA synthesis and repair, making them attractive targets for radiosensitization. B-OT acts as a prodrug, releasing oxythiamine (OT), which is further metabolized into oxythiamine pyrophosphate. This metabolite inhibits thiamine pyrophosphate-dependent enzymes, such as transketolases. By interfering with DNA repair, B-OT was hypothesized to increase the sensitivity of tumor cells to radiation.
The patient received four cycles of 177Lu-PRLT with B-OT and tolerated the treatment well, experiencing no significant changes in laboratory results and reporting improvement in clinical symptoms. Imaging after two cycles of B-OT-PRLT revealed regression of metastases compared to imaging performed before B-OT-PRLT. Additionally, the patient’s PSA levels declined substantially after just one cycle of B-OT-PRLT. Remarkably, despite the significant disease progression observed before the initiation of B-OT-PRLT, the patient survived for an additional 12 months.
This case report provides preliminary evidence suggesting that the combination of 177Lu-PRLT with B-OT could be a safe and potentially effective treatment strategy for patients with radiation-refractory mCRPC. The positive safety profile of B-OT, as demonstrated in a Phase 1 clinical trial involving healthy volunteers, further supports its potential for clinical application. While this report focuses on a single patient, the results are encouraging and warrant further investigation. A Phase 1b/2 clinical trial is planned to evaluate the safety, tolerability, and efficacy of B-OT as a radiosensitizer in combination with various radioligand therapies.

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