Introduction: Prostate adenocarcinoma represents a leading cause of cancer-related mortality. Increased emphasis on understanding the molecular basis of prostate cancer has identified a substantial burden of homologous recombination (HR) pathway mutations, which are enriched in castrate-resistant disease. This discovery has yielded novel therapeutic opportunities.
Areas covered: We will discuss the treatment of castrate-resistant prostate cancer (CRPC), with a focus on the use of poly (ADP-ribose) polymerase (PARP) inhibitors in this space. Evidence for use in HR-deficient patients will be outlined with discussion of the mechanism of action for this drug class, pathways of resistance, and approaches for expanding PARP inhibitor use to non–HR-deficient prostate cancer subgroups.
Expert opinion: PARP inhibition represents an exciting tool for management of HR-inactivated CRPC. With rapid adoption of next-generation sequencing technologies and other molecular techniques, the number of patients in this category is likely to increase. Ongoing and future investigations will be critical for improved understanding of the promise and appropriate treatment sequencing of PARP inhibition and optimal options for HR-proficient and -deficient prostate cancer populations. Questions remain about the clinical significance of monoallelic vs. biallelic HR mutations, the relevance of germline vs. somatic-only mutations, and the importance of mutations in non-canonical HR genes. 相似文献
Treatment landscape in prostate cancer has changed dramatically with the emergence of new medicines in the past few years. The traditional survival partition model (SPM) cannot accurately predict long-term clinical outcomes because it is limited by its ability to capture the key consequences associated with this changing treatment paradigm. The objective of this study was to introduce and validate a discrete-event simulation (DES) model for prostate cancer.
Methods
A DES model was developed to simulate overall survival (OS) and other clinical outcomes based on patient characteristics, treatment received, and disease progression history. We tested and validated this model with clinical trial data from the abiraterone acetate phase III trial (COU-AA-302). The model was constructed with interim data (55% death) and validated with the final data (96% death). Predicted OS values were also compared with those from the SPM.
Results
The DES model’s predicted time to chemotherapy and OS are highly consistent with the final observed data. The model accurately predicts the OS hazard ratio from the final data cut (predicted: 0.74; 95% confidence interval [CI] 0.64–0.85 and final actual: 0.74; 95% CI 0.6–0.88). The log-rank test to compare the observed and predicted OS curves indicated no statistically significant difference between observed and predicted curves. However, the predictions from the SPM based on interim data deviated significantly from the final data.
Conclusions
Our study showed that a DES model with properly developed risk equations presents considerable improvements to the more traditional SPM in flexibility and predictive accuracy of long-term outcomes. 相似文献
To determine the optimal antibiotic prophylaxis strategy for transrectal prostate biopsy (TRPB) as a function of the local antibiotic resistance profile.
Methods
We developed a decision-analytic model to assess the cost-effectiveness of four antibiotic prophylaxis strategies: ciprofloxacin alone, ceftriaxone alone, ciprofloxacin and ceftriaxone in combination, and directed prophylaxis selection based on susceptibility testing. We used a payer’s perspective and estimated the health care costs and quality-adjusted life-years (QALYs) associated with each strategy for a cohort of 66-year-old men undergoing TRPB. Costs and benefits were discounted at 3% annually. Base-case resistance prevalence was 29% to ciprofloxacin and 7% to ceftriaxone, reflecting susceptibility patterns observed at the Minneapolis Veterans Affairs Health Care System. Resistance levels were varied in sensitivity analysis.
Results
In the base case, single-agent prophylaxis strategies were dominated. Directed prophylaxis strategy was the optimal strategy at a willingness-to-pay threshold of $50,000/QALY gained. Relative to the directed prophylaxis strategy, the incremental cost-effectiveness ratio of the combination strategy was $123,333/QALY gained over the lifetime time horizon. In sensitivity analysis, single-agent prophylaxis strategies were preferred only at extreme levels of resistance.
Conclusions
Directed or combination prophylaxis strategies were optimal for a wide range of resistance levels. Facilities using single-agent antibiotic prophylaxis strategies before TRPB should re-evaluate their strategies unless extremely low levels of antimicrobial resistance are documented. 相似文献
AIM: The aim of the present study was to clinically evaluate the oral mucosa lesions of leprosy patients during and after multi-drug therapy. METHODS: Clinical examination, medical and dental history examination was performed in 100 leprosy patients. RESULTS: The results revealed that 71 patients, 50 men and 21 women, exibited oral lesions. The most frequent lesions were: fissured tongue (18 cases), inflammatory papillary hyperplasia (16 cases), chronic atrophic candidiasis (10 cases), fibroma (10 cases), erythematous candidiasis (eight cases), and traumatic ulceration (seven cases). CONCLUSION: We conclude that leprosy-related lesions are not present in patients undergoing treatment for leprosy, probably due to response to multidrug therapy. 相似文献
OBJECTIVE: We report a prospective investigation of the correlation between pretreatment Doppler vascular density (DVD) of the entire prostate gland and subsequent prostate-specific antigen (PSA) response following external beam radiation therapy, for patients with low- or intermediate-risk prostate cancer. This report updates a previous report (Sehgal et al., Acad Radiol 2003;10:366) with longer patient follow-up and additional quantitative and clinically relevant end points. METHODS: Before radiation therapy, we imaged 12 patients with transrectal Doppler sonography and measured the mean DVD of the prostate for each. For analysis, patients were separated into 3 groups by low, intermediate, and high DVD. The mean DVD for each group was linearly correlated with mean values for time above a PSA threshold of 1.0 ng/ml, post-therapy plateau PSA, and nadir PSA. RESULTS: We previously observed that pretreatment mean DVD had a strong inverse correlation with initial rate of post-therapy decline in PSA. With substantially longer follow-up on the same cohort of patients (median, 52 months), we now observe that pretreatment mean DVD also correlates with post-therapy nadir PSA (R = 0.94) and with time above a PSA threshold of 1.0 ng/mL (R = 0.99). CONCLUSION: The results of the current study are consistent with our earlier suggestion that pretreatment measurement of DVD of the entire prostate gland may be a clinically useful prognostic indicator in early prostate cancer treated with radiation. However, additional data from larger numbers of patients are needed to draw firm conclusions. 相似文献
目的研究华蟾素注射液辅助治疗前列腺癌的临床疗效。方法收集2015年1月—2017年2月襄阳市中心医院(湖北文理学院附属医院)肿瘤科收治的前列腺癌患者110例,随机分为对照组和治疗组,每组各55例。对照组患者给予相应的放化疗治疗。治疗组在放化疗开始时即静脉滴注华蟾素注射液,10~20 m L稀释于5%葡萄糖注射液250 m L中,连续用药6 d,停药1 d。连续用药3周为1个疗程,共治疗4个疗程。观察两组的临床疗效,比较两组治疗前后血清前列腺特异抗原(PSA)水平和毒副反应。结果治疗后,对照组客观缓解率(ORR)是69.09%,临床获益率(CBR)是85.45%;治疗组ORR是89.09%,CBR是96.36%,两组ORR、CBR比较差异有统计学意义(P0.05)。治疗后,两组患者血清PSA水平均显著降低,同组治疗前后差异有统计学意义(P0.05);治疗后,治疗组血清PSA水平显著低于对照组,两组比较差异有统计学意义(P0.05)。治疗组患者白细胞减少、恶心呕吐的发生率明显低于对照组,两组比较差异有统计学意义(P0.05)。结论华蟾素注射液辅助治疗前列腺癌临床疗效确切,能显著降低血清PSA水平,减少患者白细胞降低和恶心呕吐的发生率,具有一定的临床推广应用价值。 相似文献