Estramustine Phosphate Sodium

Prostate cancer antigen-1/ALKBH3, a DNA/RNA demethylase of 3-methylcytosine, 1-methyladenine (1-meA), and 6-meA, was found in prostate cancer as an important prognostic factor. Additionally, 1-meA has been associated with other cancers. The ALKBH3 inhibitor HUHS015 was found to be effective against prostate cancer both in vitro and in vivo. Herein, we investigated the effect of HUHS015 in combination with drugs for prostate cancer approved in Japan (including bicalutamide, cisplatin, mitoxantrone, prednisolone, ifosfamide, tegafur/uracil, docetaxel, dacarbazine, and estramustine) by treating DU145 cells with around IC50 value concentrations of these drugs for 3 days. Additionally, the cells were observed for additional 9 days after drug removal. Combination treatment with dacarbazine, estramustine, tegafur/uracil, and HUHS015 showed a slight additive effect after 3 days. After drug washout of them and mitoxantrone, the combined effects and levels were enhanced and sustained, although the effects of each treatment alone declined. HUHS015 combined with cisplatin or docetaxel elicited synergistic and sustained effects. In vivo, combining HUHS015 and docetaxel, the first chemotherapeutic agent for castration-resistant prostate cancer, showed notable effects in the DU145 xenograft model. In conclusion, HUHS015 exhibited a synergistic effect with docetaxel and drugs acting on DNA in vitro, even after drug removal. Since cancer chemotherapy is typically administered during rest periods due to its high toxicity, combining it with an ALKBH3 inhibitor could be a promising strategy for enhancing cancer treatment, as it can elicit an additive effect during treatment, allowing dosage reduction, and synergistically sustain the effect after drug washout during rest periods.

We aimed to examine trends in novel antiandrogen receptor signal inhibitor (ARSI) usage and medical costs by collecting real‐world big data included in The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data, covering most of the clinical practices throughout Japan.

Usage data for outpatient prescriptions from 2016 to 2021 were extracted from the NDB Open Data. Among the 459,610 million tablets/capsules prescribed, prostate cancer‐specific agents (bicalutamide, estramustine phosphate, flutamide, abiraterone, enzalutamide, apalutamide, and darolutamide) were selected to investigate the trends of usage and medical costs.

In total, 764.8 billion medications were recorded. Among these, standard dose‐adjusted prescriptions for bicalutamide, abiraterone, enzalutamide, apalutamide, darolutamide, and other vintages (estramustine phosphate, flutamide) was 276, 14.2, 18.1, 2.19, 0.34, and 20.3 million, respectively. The usage of ARSI increased significantly from 6.1% in 2016 to 16% in 2021. The medical costs for prostate cancer‐specific agents increased significantly (1.8‐fold) from 2016 to 2021. Despite the limited usage of ARSIs, a majority of the medical costs had been spent on ARSIs. Medical costs associated with ARSIs increased significantly from 59% to 89% (p < 0.001).

ARSI usage and medical costs associated with prostate cancer increased significantly from 2016 to 2021. Despite the limited use of ARSIs, a considerable proportion of the medical costs for prostate cancer‐specific agents had been spent on ARSIs.