Chinese Medicines in the Treatment of Prostate Cancer: From Formulas to Extracts and Compounds.

Focal Therapy for Localized Prostate Cancer: A Critical Appraisal of Rationale and Modalities

COMPLETE ANDROGEN BLOCKADE FOR PROSTATE CANCER: WHAT WENT WRONG?

Prostate cancer (PCa) is a common disease among men worldwide, and conventional treatments for PCa typically involve surgery, chemotherapy, and radiation therapy. However, Chinese medicine (CM) has gained increasing attention as a complementary therapy for PCa treatment in recent decades. Chinese herbal medicine (CHM), a form of CM, has been shown to have good potential in PCa treatment, particularly by targeting the androgen receptor (AR), which plays a critical role in the development and progression of PCa. CHM interventions have been shown to inhibit AR activity, thereby delaying the disease’s progression. Moreover, most PCa patients at a later stage usually develop castration-resistant disease and drug resistance, posing a daunting challenge to clinical treatment. CHM offers several advantages, including improvement of patients’ quality of life, amelioration of clinical symptoms, and prolongation of survival; therefore, it offers a new direction for PCa treatment. This review aims to examine the current literatures on CM interventions targeting AR in PCa treatment. The review provides valuable insights into the potential benefits of CM as a complementary therapy for PCa treatment.

Prostate cancer is the most common cancer in men. In China, traditional Chinese medicine is used to treat prostate cancer. However, there is a lack of evidence for differences in the effectiveness and safety of different Chinese patent medicines. Therefore, we conducted this Network Meta-analysis to investigate the efficacy and safety of different Chinese patent medicines in the treatment of prostate cancer. We systematically search PubMed, Web of Science, Embase, Cochrane library, CNKI database, VIP database, wanfang database, and SinoMed Randomized controlled trials of Chinese patent medicines for the treatment of prostate cancer sores included in the database were retrieved until June 1, 2023. The included studies were assessed for risk of bias using Cochrane randomized controlled trial Bias risk Assessment tool. The main outcome indicators were Efficacy, Prostate Specific Antigen, and adverse reaction. Since different courses of treatment were used in the included studies, we used Bayesian mesh meta-regression to investigate the effects of treatment courses on efficacy and safety. Twenty-seven articles were included, involving 1885 patients. Including 9 kinds of Chinese patent medicine. The results of Network Meta-analysis show that: ① efficacy: compared with androgen antagonists, Bruceolic oil emulsion (relative risk = 1.70, 95% credibility interval [CI] (1.30, 2.29)), Compound Kushen injection (relative risk = 1.39, 95%CI (1.19, 1.70)) had significant advantages. There was no significant difference among all Chinese patent medicines (P > .05). The top 3 Chinese patent medicines were Bruceolic oil emulsion, Zhibodihuang pill, Compound Kushen injection. ② Prostate specific antigen: compared with androgen antagonists, Bruceolic oil emulsion (mean difference [MD] = -10.4, 95%CI [-17.6, -3.21]), Compound Kushen injection (MD = -4.46, 95%CI [-8.80, -1.70]), Shenfu injection (MD = -14.7, 95%CI [-23.4, -6.01]) had significant advantages. The top 3 Chinese patent medicines were Shenfu injection, Bruceolic oil emulsion, Compound Kushen injection. adverse reaction: compared with androgen antagonists, there was no significant difference among all PCM (P > .05). Compared with androgen antagonists, Chinese patent medicine has significant difference in effectiveness. The effect of Chinese patent medicine is little affected by the course of treatment and dose. From comprehensive analysis, Bruceolic oil emulsion combined with androgen antagonist is the best intervention measures.

Prostate cancer is the second-leading cause of cancer death in American men. Current therapeutic approaches have made significant progression in the control of prostate cancer progression. On the other hand, conventional therapeutics have variable efficacies and are usually associated with metastatic recurrence and/or high cytotoxicity. Therefore the search for effective chemopreventive agents with minimal side effects has remained one of the top priorities in prostate cancer research. Some Chinese herbal medicines have been used for centuries, thus certain Chinese medicines with active anti-cancer ingredients may be effective candidates for the prevention and/or treatment of prostate cancer. Danshen (Salvia miltiorrhiza) has been widely adopted in the traditional Chinese medicinal preparations for treatment of cerebrovascular disorders with minimal side effects. We thus evaluated the effects of several major Danshen components, tanshinones IIA (T2A), tanshinone I (T1) and cryptotanshinone (CT) on the growth of prostate cancer cells and identified the potential molecular targets that were responsive to and might be responsible for the treatments. CT, T2A and T1 significantly inhibited the growth of prostate cancer cells with the IC50s at a few Ms associated with cell cycle arrests and apoptosis induction in vitro, whereas their growth inhibition effects on normal prostate epithelial cells were dramatically reduced by 5–10 folds. T1 showed the most potent activity among the three compounds, but the combination of CT and T2A showed synergistic effects against prostate cancer cell growth. The pilot animal study verified that T1 inhibited the growth of DU145 tumors in a dose-dependent manner. By using the real time PCR arrays for epigenetic markers, we identified Aurora A kinase gene as a potential molecular target of tanshinones. Aurora A gene and protein were up-regulated in prostate cancer cell lines when compared with that in the normal cells, and the tanshinone treatments significantly down-regulated its expression. These results demonstrated potent anti-prostate cancer activities of tanshinones and identified Aurora A as a potential molecular target of tanshinones actions. Further in vivo studies of the chemopreventive effects of tanshinones and the CT and T2A combination on prostate cancer development and/or progression are warranted. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A75.

Acute and Late Toxicity in High-risk Prostate Cancer Treated with Androgen Suppression and Hypofractionated Intensity Modulated Radiotherapy

Late Toxicity in High-risk Prostate Cancer Treated with Androgen Suppression and Hypofractionated Intensity Modulated Radiotherapy

PurposeTo define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method.MethodsA panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings.ResultsThirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation.ConclusionFocal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.

Objective To evaluate the real world data on toxicity and quality of life of patients after treatment for prostate cancer in China. Methods Electronic questionnaires were issued to members of the prostate cancer patient group in Beijing through the network new media method to collect the basic information of these patients, diagnostic information, TNM stage, treatment options, and adverse reactions after therapy. The questionnaire were designed based on the EORTC C30 and PR25. Systemic reactions, urinary reactions, rectal reactions, hematology toxicity, and sexual dysfunction were analyzed using the Pearson χ2 test, and Fisher′s exact test was used when the probability frequency was less than 5. Results A total of 228 patients were included. The proportions of patients who underwent radical, external radiotherapy (including postoperative radiotherapy), endocrine therapy, chemotherapy, and particle implantation were 50.0% (114/228), 77.6% (177/228), 80.3% (183/228), 7.89% (18/228), and 3.95% (9/228), respectively. Top ten treatment toxicities were fatigue (42.5%, 97/228), defecation frequency (42.1%, 96/228), leukopenia (39.5%, 90/228), urinary frequency (31.6%, 72/228), increased nocturia (27.6%, 63/228), anemia (20.2%, 46/228), diarrhea (19.7%, 45/228), urinary urgency (19.7%, 45/228), sexual dysfunction (18.4%, 42/228), and sleep loss (18.4%, 42/228). The incidence of urinary incontinence (23.7% vs 5%, χ2=12.200, P=0.000) and sexual dysfunction (21.1% vs 15%, χ2=1.140, P=0.286) in patients undergoing surgery was higher than that of patients undergoing radiotherapy. The rates of urinary frequency (32.5% vs 30.7%, χ2=0.071, P=0.791) and defecation frequency (45% vs 34.2%, χ2=2.310, P=0.286) in patients undergoing radiotherapy were higher than those in patients undergoing surgery. To treat these adverse reactions, the first choice in these patients was to take traditional Chinese medicine (46.9%, 107/228). Conclusion Different treatment methods have different toxicities and different effects on quality of life, and reasonable treatment plan should be chosen according to patients′ demands for future quality of life. Key words: Prostate cancer; Radiotherapy; Oppenheimer′s treatment; Quality of life

When and How to Use PARP Inhibitors in Prostate Cancer: A Systematic Review of the Literature with an Update on On-Going Trials

Chinese medicines as therapeutic options for treating prostate cancer: Therapeutic effects and underlying mechanisms.

The incidence of prostate cancer is gradually increasing. There are many methods for clinical treatment of prostate cancer, such as surgical treatment and endocrine treatment. In the case of advanced prostate cancer, we must not only extend patients' survival times but also enhance their quality of life. Endocrine medications are the most effective therapy for advanced prostate cancer. This research will investigate the therapeutic impact of a complete treatment model in prostate cancer in order to discover a trustworthy clinical treatment model. This research discovered that, as compared to endocrine treatment, radical resection of prostate cancer may diminish and reach lower serum PSA levels in a short amount of time, as well as sustain low PSA levels and delay progression to castration resistance. Moreover, the comprehensive treatment mode can effectively reduce the possibility of complications. The research results show that the comprehensive treatment model can play an important role in the treatment of prostate cancer.

Taiwan National Health Insurance (NHI) provides Western medicine and Chinese medicine (CM). This study aims to explore the trends of CM use among prostate cancer patients under NHI. Claims of CM outpatient services from 1996 to 2008 were obtained from NHI Research Database. CM visits of prostate cancer patients were identified. Claims with diagnosis code of prostate cancer were defined as cancer-specific visits. Among 78 323 prostate cancer patients identified during 1996-2008, there were 30 383 (38.8%) CM users and 327 063 CM outpatient visits. The prevalence of CM use in each cross-sectional year increased slightly from 24.9% to 25.6%. Most CM visits (92.7%) were non-cancer-specific. There were greater increases in the proportion of cancer-specific CM visits (from 2.3% to 10.6%) and high-utility CM users (from 3.1% to 19.7%). Most CM services were provided by private clinics (68.1% to 79.2%). The most frequently used CM therapies were Chinese herbal medicine (72.8% to 78.8%), followed by acupuncture/traumatology manipulative therapies (28.1% to 36.8%). Total CM cost increased from $122 247 to $825 454. The average cost per CM visit increased from $14.0 to $19.6. The annual cost per CM user increased from $88.0 to $134.4. Copayment accounted for 6.6% to 11.7%. There was a trend of increased CM use among prostate cancer patients under NHI. Although prostate cancer patients used CM mostly for noncancer diseases, CM visits for prostate cancer increased remarkably. The utilization patterns of CM visits for cancer and for noncancer diseases were distinctly different.

Prostate cancer is a leading cause of death in men worldwide. For over 30 years, growing interest has focused on the development of vaccines as treatments for prostate cancer, with the goal of using vaccines to activate immune cells capable of targeting prostate cancer to either eradicate recurrent disease or at least delay disease progression. This interest has been prompted by the prevalence and long natural history of the disease and by the fact that the prostate is an expendable organ. Thus, an immune response elicited by vaccination might not need to target the tumour uniquely but could theoretically target any prostate tissue. To date, different vaccine approaches and targets for prostate cancer have been evaluated in clinical trials. Overall, five approaches have been assessed in randomized phase III trials and sipuleucel-T was approved as a treatment for metastaticcastration-resistant prostate cancer, being the only vaccine approved to date by the FDA as a treatment for cancer. Most vaccine approaches showed safety and some evidence of immunological activity but had poor clinical activity when used as monotherapies. However, increased activity has been observed when these vaccines were used in combination with other immune-modulating therapies. This evidence suggests that, in the future, prostate cancer vaccines might be used to activate and expand tumour-specific T cells as part of combination approacheswith agents that target tumour-associated immune mechanisms of resistance.

Purpose. Zoledronic acid is widely accepted as the treatment of choice for a number of cancers which metastasise to bone and is the only bisphosphonate licensed for the treatment of prostate cancer. However, drug related nephrotoxicity, although rare, does pose a significant complication when using zoledronic acid. Prostate cancer patients are generally older than 65 years of age and already exhibit some form of impaired renal function. Thus, for prostate cancer patients who are unable to tolerate zoledronic acid there is a need for an alternative bisphosphonate. One possibility could be ibandronate which is also a potent third generation, nitrogen-containing bisphosphonate and is an attractive choice for some patients due to the fact it is available in both intravenous and oral preparations. Methods. This article reviews the current published literature regarding the use of ibandronate in the treatment of metastatic prostate cancer. Results. Preliminary data emerging from small Phase II studies suggests ibandronate may provide a therapeutic alternative for the treatment of metastatic prostate cancer when zoledronic acid is deemed unsuitable. Conclusion. Further in vivo research with ibandronate in prostate cancer is urgently needed in order to elucidate whether this bisphosphonate may play a role in the treatment and palliative management of metastatic prostate cancer.