• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.3
• /
• pp.1313-1320
• /
• 2014

Introduction: Although most prostate cancers initially respond to castration with luteinizing hormonereleasing analogues or bilateral orchiectomy, progression eventually occurs. Based on the exciting results of several randomized controlled trials (RCTs), it seems that patients with metastatic castration-resistant prostate cancer (mCRPC) might benefit more from treatment withabiraterone. Therefore we conducted a systematic review to evaluate the efficacy and toxicity of abiraterone in the treatment of mCRPC. Methods: Literature was searched from Embase, PubMed, Web of Science, and Cochrane Library up to July, 2013. Quality of the study was evaluated according to the Cochrane's risk of bias of randomized controlled trial (RCT) tool, then the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System was used to rate the level of evidence. Stata 12.0 was used for statistical analysis. Summary data from RCTs comparing abiraterone plus prednisone versus placebo plus prednisone for mCRPC were meta-analyzed. Pooled hazard ratios (HRs) for overall survival (OS), radiographic progression-free survival (RPFS) and time to PSA progression (TTPP); Pooled risk ratios (RR) for PSA response rate, objective response rate and adverse event were calculated. Results: Ten trials were included in the systematic review; Data of 2,283 patients (1,343 abiraterone; 940 placebo) from two phase 3 trials: COU-AA-301 and COU-AA-302 were meta-analyzed. Compared with placebo, abiraterone significantly prolonged OS (HR, 0.74; 95% confidence interval [CI], 0.66 to 0.84), RPFS (HR, 0.59; 95% CI, 0.48 to 0.74) and time to PSA progression (HR, 0.55; 95% CI, 0.43 to 0.70); it also significantly increased PSA response rate (RR, 3.63; 95% CI, 1.72 to 7.65) and objective response rate (RR, 3.05; 95% CI, 1.51 to 6.15). This meta-analysis suggested that the adverse events caused by abiraterone are acceptable and can be controlled. Conclutios: Abiraterone significantly prolonged OS, RPFS and time to progression patients with mCRPC, regardless of prior chemotherapy or whether chemotherapy-na$\ddot{i}$ve, and no unexpected toxicity was evident. Abiraterone can serve as a new standard therapy for mCRPC.

• Korean Journal of Radiology
• /
• v.25 no.2
• /
• pp.179-188
• /
• 2024

Objective: ¹⁷⁷Lutetium [Lu] Ludotadipep is a novel prostate-specific membrane antigen targeting therapeutic agent with an albumin motif added to increase uptake in the tumors. We assessed the biodistribution and dosimetry of [¹⁷⁷Lu]Ludotadipep in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods: Data from 25 patients (median age, 73 years; range, 60-90) with mCRPC from a phase I study with activity escalation design of single administration of [¹⁷⁷Lu]Ludotadipep (1.85, 2.78, 3.70, 4.63, and 5.55 GBq) were assessed. Activity in the salivary glands, lungs, liver, kidneys, and spleen was estimated from whole-body scan and abdominal SPECT/CT images acquired at 2, 24, 48, 72, and 168 h after administration of [¹⁷⁷Lu]Ludotadipep. Red marrow activity was calculated from blood samples obtained at 3, 10, 30, 60, and 180 min, and at 24, 48, and 72 h after administration. Organand tumor-based absorbed dose calculations were performed using IDAC-Dose 2.1. Results: Absorbed dose coefficient (mean ± standard deviation) of normal organs was 1.17 ± 0.81 Gy/GBq for salivary glands, 0.05 ± 0.02 Gy/GBq for lungs, 0.14 ± 0.06 Gy/GBq for liver, 0.77 ± 0.28 Gy/GBq for kidneys, 0.12 ± 0.06 Gy/GBq for spleen, and 0.07 ± 0.02 Gy/GBq for red marrow. The absorbed dose coefficient of the tumors was 10.43 ± 7.77 Gy/GBq. Conclusion: [¹⁷⁷Lu]Ludotadipep is expected to be safe at the dose of 3.7 GBq times 6 cycles planned for a phase II clinical trial with kidneys and bone marrow being the critical organs, and shows a high tumor absorbed dose.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.3
• /
• pp.1285-1290
• /
• 2014

The aim was to determine whether ultrasound targeted microbubble destruction (UTMD) promotes dual targeting of HSP72 and HSC70 for therapy of castration-resistant prostate cancer (CRPC), to improve the specific and efficient delivery of siRNA, to induce tumor cell specific apoptosis, and to find new therapeutic targets specific of CRPC.VCaP cells were transfected with siRNA oligonucleotides. HSP70, HSP90 and cleaved caspase-3 expression were determined by real-time quantitative polymerase chain reaction and Western blotting. Apoptosis and transfection efficiency were assessed by flow cytometry. Cell viability assays were used to evaluate safety. We found HSP72, HSC70 and HSP90 expression to be absent or weak in normal prostate epithelial cells (RWPE-1), but uniformly strong in prostate cancerous cells (VCaP). UTMD combined with dual targeting of HSP72 and HSC70 siRNA improve the efficiency of transfection, cell uptake of siRNA, downregulation of HSP70 and HSP90 expression in VCaP cells at the mRNA and protein level, and induction of extensive tumor-specific apoptosis. Cell counting kit-8 assays showed decreased cellular viability in the HSP72/HSC70-siRNA silenced group. These results suggest that the combination of UTMD with dual targeting HSP70 therapy for PCa may be most efficacious, providng a novel, reliable, non-invasive, safe targeted approach to improve the specific and efficient delivery of siRNA, and achieve maximal effects.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.20 no.1
• /
• pp.28-31
• /
• 2016

Purpose $^{223}Ra-Dichloride$ is used for the medicine of castration-resistant prostate cancer (CRPC) and which emits ${\alpha}-ray$ of 28 Mev that is used for therapy. However $^{223}Ra-Dichloride$ emits ${\beta}-ray$ of 3.6% and ${\gamma}-ray$ of 1.1%(80,156,270 keV) aside from ${\alpha}-ray$ in decay. Therefore we would like to evaluate external radiation expose dose rate of ${\gamma}-ray$ of $^{223}Ra-Dichloride$. Materials and Methods We calculated external radiation expose dose rate using ${\gamma}-constant$ of $^{223}Ra-Dichloride$, $^{99m}Tc$ based on Health physics(2012). $^{223}Ra-Dichloride$ of 3.5 MBq and $^{99m}Tc-MDP$ of 740 MBq were applied. external radiation expose dose rate 15 times from 1m by survey meter. Results ${\gamma}-contant$ of $^{223}Ra$, $^{99m}Tc-MDP$ from 1m distance based on Health physics(2012) is 0.0469, 0.0215. calculated value of external radiation expose dose rate was $16{\mu}Sy$, $34{\mu}Sy$ which activity is $^{223}Ra-Dichloride$ of 3.5 MBq and $^{99m}Tc-MDP$ of 740 MBq from 1 m and measured mean value of 1 m was $0.7{\mu}Sy/h$, $18{\mu}Sy/h$. Conclusion ${\gamma}-constant$ of $^{223}Ra$ is higher than $^{99m}Tc$ based on Health physics(2012). however calculated maximum external radiation expose dose rate of $^{223}Ra-Dichloride$ is lower than $^{99m}Tc$ due to actually used quantity of activity of $^{223}Ra-Dichloride$ is small. measured value of $^{223}Ra-Dichloride$ is also lower than $^{99m}Tc-MDP$. Therefore external radiation expose dose rate of ${\gamma}-ray$ of $^{223}Ra-Dichloride$ is very low.