Bipolar androgen therapy (BAT), as a new therapeutic strategy for castration-resistant prostate cancer (CRPC), can significantly reduce the level of prostate-specific antigen (PSA) for prostate cancer patients and has exhibited an excellent safety profile with no serious adverse events. Based on the clinical trials recently published at home and abroad, this article reviews the background, action mechanism, development, and prospect of BAT.
Androgen Antagonists ; therapeutic use ; Hormone Replacement Therapy ; methods ; Humans ; Male ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms, Castration-Resistant ; blood ; drug therapy ; Receptors, Androgen ; Testosterone ; administration & dosage ; blood

OBJECTIVETo investigate the safety and medication cycles of intermittent androgen deprivation (IAD) in the treatment of aggressive prostate cancer.

METHODSBased on prostate cancer clinical staging, we divided 178 patients with aggressive prostate cancer into groups A (T3-4N0M0), B (TXN1M0) and C (TXNXM1) to receive maximum androgen blockage for at least 6 months till the PSA level remained at < or = 0.2 microg/L for 3 months, followed by an off-period (without medication). The on-period was initiated when the PSA level was > 4 microg/L, and then stopped again when it was < or = 0.2 microg/L. We recorded and compared the patients' age, baseline PSA levels, Gleason scores, duration of on- and off-period, and time to tumor progression.

RESULTSThe baseline PSA levels of the 3 groups were (27.5 +/- 14.6), (43.4 +/- 21.8) and (62.8 +/- 44.6) microg/L, P < 0.01; the follow-ups averaged (38.4 +/- 9.6), (33.1 +/-14.0) and (28.3 +/- 14.3) months; and the times from medication initiation to tumor progression were (37.4 +/- 6.6), (27.4 +/- 10.2) and (16.6 +/- 4.4) months, respectively. Group A showed a longer off-period and more medication cycles than B and C (P < 0.01). Nineteen patients completed 5 cycles and 2 died of cardiovascular events in group A. PSA elevation and cancer progression occurred after 3 cycles at most in group C. Six died in group B, 1 of metastatic prostate cancer, and 36 died in group C, 21 of metastasis.

CONCLUSIONFor local aggressive prostate cancer, IAD can effectively slow down tumor progression, reduce adverse events and improve patients' quality of life.

Aged ; Aged, 80 and over ; Androgen Antagonists ; administration & dosage ; therapeutic use ; Antineoplastic Agents, Hormonal ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Prostatic Neoplasms ; drug therapy ; Treatment Outcome

INTRODUCTIONThe advent of prostate specific antigen (PSA) has resulted in an increased incidence of early detection of prostate cancer recurrence. Patients treated with androgen deprivation therapy (ADT) become hormone-resistant after 18 to 24 months. In patients with biochemical failure, where there is a rise in PSA but no objective evidence of metastases, or in whom there are small volume metastases but who are asymptomatic, there is no standard of care after ADT. Ketoconazole, an antimycotic which affects the synthesis of androgens and other steroids, has shown direct cytotoxic effects in prostate cancer cell lines in in-vitro studies. This study describes our experience with ketoconazole treatment for hormone refractory prostate cancer (HRPC).

MATERIALS AND METHODSA retrospective study of HRPC patients given ketoconazole at the National Cancer Centre and The Cancer Institute from 2004 to 2005 was performed. All eligible patients had histologically proven adenocarcinoma of the prostate and a rising PSA level despite ADT with orchidectomy or luteinising hormone-releasing hormone (LHRH) agonist therapy. All patients received 200 mg of ketoconazole thrice daily. Response was defined as a decline in PSA of at least 50% from the pre-treatment level and confirmed by a second PSA value 4 or more weeks later. The endpoints evaluated were the presence and duration of a response and the toxicity profile of the treatment.

RESULTSA total of 32 patients with HRPC were treated with ketoconazole. Twelve (38%) of the 32 patients had a greater than 50% decrease in their PSA values. The median duration of response was 6.75 months. The median time to reach PSA nadir was 3.5 months. Five patients continue to exhibit progression-free response at the time of writing. Ketoconazole was generally well tolerated. Eighteen (56%) patients recorded mild toxicities related to ketoconazole. There were no grade 3 or 4 toxicities.

CONCLUSIONSLow-dose ketoconazole bridges the gap in the continuum of treatment for patients who have failed ADT and in whom cytotoxic chemotherapy would have a significant impact on the quality of life. Its good toxicity profile, low cost and ease of administration makes it a viable option for this group of patients.

Adenocarcinoma ; Aged ; Aged, 80 and over ; Androgen Antagonists ; administration & dosage ; therapeutic use ; Androgens ; biosynthesis ; Humans ; Ketoconazole ; administration & dosage ; pharmacology ; Male ; Middle Aged ; Prostate-Specific Antigen ; Prostatic Neoplasms ; drug therapy ; Retrospective Studies ; Singapore

Abortifacient Agents, Steroidal ; administration & dosage ; Abortion, Induced ; methods ; Androgen Antagonists ; administration & dosage ; Contraceptives, Oral ; administration & dosage ; Female ; Fertilization in Vitro ; methods ; Gonadotropin-Releasing Hormone ; administration & dosage ; analogs & derivatives ; Hormone Replacement Therapy ; methods ; Hormones ; administration & dosage ; Humans ; Mifepristone ; administration & dosage ; Norpregnenes ; administration & dosage ; Pregnancy

OBJECTIVETo search for an effective hormonal therapy for delaying the progression of prostate cancer to androgen-independent prostate cancer (AIPC).

METHODSThis study included 93 cases of prostate cancer confirmed by transrectal ultrasound-guided biopsy, 22 treated by bilateral orchiectomy plus bicalutamide as a continuous androgen deprivation (CAD) therapy, and the other 71 by the intermittent androgen deprivation (IAD) therapy, the latter divided into a standard IAD group (n = 29) and a modified IAD group (n = 42) to be treated by maximum androgen blockage (MAB) until the serum PSA level decreased to less than 0.2 microg/L and the medication was maintained for 3 months. Entering the intermittent period, the patients of the standard IAD group discontinued medication, while those in the modified IAD group withdrew luteinizing hormone-releasing hormone analogue (LHRH-a) but continued the use of bicalutamide. MAB was resumed in these two groups when serum PSA manifested a continuous rise and went up to 4 microg/L until prostate cancer progressed to AIPC. Comparisons were made among the CAD, standard IAD and modified IAD groups in the follow-up time, time of progression to CRPC and treatment cycles.

RESULTSThe three groups of patients were well balanced in terms of demographics, baseline characteristics and follow-up time. The median times of progression to AIPC in the CAD, standard IAD and modified IAD groups were (26.50 +/- 4.15), (30.00 +/- 7.83) and (34.93 +/- 5.08) months, respectively, with statistically significant differences between the modified IAD group and the CAD (P = 0.001) and standard IAD (P = 0.032), but not between the latter two groups (P = 0.143). Kaplan-Meier survival curves showed a significantly longer median time of progression to AIPC in the modified than in the standard IAD group (P = 0.01). The mean cycle length was (16.13 +/- 3.33) months for the standard IAD group and (19.58 +/- 4.30) months for the modified IAD group, and the time off treatment of the first cycle was (9.6 +/- 3.2) months in the former and (14.2 +/- 3.7) months in the latter, with significant difference between the two groups (P = 0.001).

CONCLUSIONCompared with CAD and standard IAD, modified IAD therapy can significantly prolong the time of progression to AIPC in patients with prostate cancer.

Aged ; Aged, 80 and over ; Androgen Antagonists ; administration & dosage ; therapeutic use ; Anilides ; administration & dosage ; therapeutic use ; Antineoplastic Agents, Hormonal ; administration & dosage ; therapeutic use ; Disease Progression ; Humans ; Male ; Middle Aged ; Nitriles ; administration & dosage ; therapeutic use ; Prognosis ; Prostatic Neoplasms ; diagnosis ; drug therapy ; Tosyl Compounds ; administration & dosage ; therapeutic use ; Treatment Outcome

PURPOSE: Few data are available concerning the clinical outcome of abiraterone acetate treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) in terms of the duration of androgen deprivation therapy (ADT) before diagnosis of CRPC. We investigated the clinical efficacy of abiraterone acetate according to the duration of ADT. MATERIALS AND METHODS: We reviewed the medical records of 20 patients with mCRPC who received abiraterone acetate after failure of docetaxel chemotherapy from May 2012 to March 2014 at Seoul National University Bundang Hospital. Clinical factors including prostate-specific antigen (PSA) nadir level, time to PSA nadir, PSA doubling time, PSA response, and modes of progression (PSA, radiologic, clinical) were analyzed. Disease progression was classified according to the Prostate Cancer Working Group 2 criteria. RESULTS: The mean age and PSA value of the entire cohort were 76.0+/-7.2 years and 158.8+/-237.9 ng/mL, respectively. The median follow-up duration was 13.4+/-6.7 months. There were no statistically significant differences in clinical characteristics between patients who received abiraterone acetate with ADT duration<35 months and those who received abiraterone acetate with ADT duration> or =35 months. There were also no significant differences in terms of PSA progression-free survival, radiologic progression-free survival, and clinical progression-free survival between patients with ADT duration<35 months and those with ADT duration > or =35 months. CONCLUSIONS: Although this was a retrospective study with a small sample size, we did not observe any statistically significant differences in the clinical response to abiraterone acetate between mCRPC patients with long ADT duration and those with short ADT duration in terms of disease progression-free survival.
Abiraterone Acetate/administration & dosage ; Aged ; Aged, 80 and over ; Androgen Receptor Antagonists/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Disease Progression ; Drug Administration Schedule ; Humans ; Kallikreins/blood ; Male ; Neoplasm Metastasis ; Prostate-Specific Antigen/blood ; Prostatic Neoplasms, Castration-Resistant/*drug therapy ; Retrospective Studies ; Taxoids/administration & dosage ; Treatment Outcome

OBJECTIVETo investigate the clinical efficacy of integrative traditional Chinese and Western medicine on polycystic ovarian syndrome (PCOC).

METHODSSixty-three patients with polycystic ovarian syndrome were randomly allocated into 2 groups, 31 patients orally administered with diane-35 in the Western medicine group (WMG) and 32 patients treated with conventional controlled medicine plus modified Yougui Pill in the integrative medicine group (IMG). Changes of relevant hormones and clinical syndromes in patients were detected before treatment, after 3 cyclic treatment and at the 6th cycle after treatment.

RESULTSThe levels of relevant hormones and the indexes of B-ultrasonic were obviously improved after treatment in the two groups. But 6 cycles after treatment, these changes restored to the baseline as those before treatment in WMG, while maintained in IMG (P < 0.01). What's more, the normalization of menstruation, ovulation and pregnancy rate in IMG were significantly higher than those in WMG (P < 0.01).

CONCLUSIONDiane-35 combined with modified yougui pill in treating polycystic ovarian syndrome not only shows marked short-term effect, but could consolidate the curative effect.

Adult ; Androgen Antagonists ; therapeutic use ; Cyproterone Acetate ; therapeutic use ; Drug Administration Schedule ; Drug Combinations ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Ethinyl Estradiol ; therapeutic use ; Female ; Humans ; Phytotherapy ; Polycystic Ovary Syndrome ; drug therapy ; Tablets

PURPOSE: To investigate the efficacy of androgen deprivation treatment (ADT) between continuous and intermittent ADT. MATERIALS AND METHODS: Between January 2006 and May 2015, 603 patients were selected and divided into continuous ADT (CADT) (n=175) and intermittent ADT (IADT) (n=428) groups. The median follow-up in this study was 48.19 (1.0-114.0) months. The primary end point was time to castration resistant prostate cancer (CRPC). The types of ADT were monotherapy and maximal androgen blockade (i.e., luteinizing hormone-releasing hormone agonist and antiandrogen). RESULTS: The characteristics of patients showed no significant differences between the CADT and IADT groups, except for the Gleason score (p<0.001). The median time to CRPC of all enrolled patients with ADT was 20.60±1.60 months. The median time to CRPC was 11.20±1.31 months in the CADT group as compared with 22.60±2.08 months in the IADT group. In multivariate analysis, percentage of positive core (p=0.047; hazard ratio [HR], 0.976; 95% confidence interval [CI], 0.953-1.000), Gleason score (p=0.007; HR, 1.977; 95% CI, 1.206-3.240), lymph node metastasis (p=0.030; HR, 0.498; 95% CI, 0.265-0.936), bone metastasis (p=0.028; HR, 1.921; 95% CI, 1.072-3.445), and CADT vs. IADT (p=0.003; HR, 0.254; 95% CI. 0.102-0.633) were correlated with the duration of progression to CRPC. The IADT group presented a significantly longer median time to CRPC compared with the CADT group. Additionally, patients in the IADT group showed a longer duration in median time to CRPC in subgroup analysis according to the Gleason score. CONCLUSIONS: This study found that IADT produces a longer duration in median time to CRPC than does CADT.
Adenocarcinoma/*drug therapy/pathology/secondary ; Aged ; Aged, 80 and over ; Androgen Antagonists/*administration & dosage/therapeutic use ; Antineoplastic Agents, Hormonal/*administration & dosage/therapeutic use ; Disease Progression ; Drug Administration Schedule ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Prostatic Neoplasms/*drug therapy/pathology ; Prostatic Neoplasms, Castration-Resistant/drug therapy/pathology ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo determine the influence of maximal androgen blockade (MAB) on bone mineral density (BMD) in men with prostate cancer.

METHODSWe enrolled 40 men with prostate cancer treated by MAB for 7 to 12 months. We obtained the laboratory results of PSA, testosterone, serum calcium and phosphorus, 24-h urine calcium and phosphorus, alkaline phosphatase, and parathyroid hormone, measured the BMD of the lumbar spine and femoral neck by dual energy X-ray absorptiometry, recorded pain scores, and compared the results before and after the treatment.

RESULTSBefore MAB treatment, 5 (12.5%) of the patients met the BMD criteria of lumbar spine (L2-4) osteopenia, 8 (20%) lumbar spine (L2-4) osteoporosis, 13 (32.5%) left femoral neck osteopenia, and 15 (37.5%) left femoral neck osteoporosis. The PSA and testosterone levels were decreased from (52.9 +/- 69.9) microg/L and (18.9 +/- 6.5) nmol/L before MAB to (1.5 +/- 1.6) microg/L and (1.9 +/- 1.3) nmol/L after it (P<0.05). There were no statistically significant differences before and after MAB in the levels of serum calcium and phosphorus, 24-h urine calcium and phosphorus, alkaline phosphatase, and parathyroid hormone (P>0.05), nor in the BMD levels of the lumbar spine ([1.1 +/- 0.1] vs [1.1 +/- 0.2] g/cm2) and femoral neck ([0.8 +/- 0.2] vs [0.8 +/- 0.1] g/cm2), nor in the pain score ([0.6 +/- 0.2] vs [0.7 +/- 0.1], P>0.05).

CONCLUSIONMAB treatment (range from 7 to 12 months) has no significant influence on BMD in men with prostate cancer, but BMD should be measured before MAB.

Aged ; Aged, 80 and over ; Alkaline Phosphatase ; analysis ; Androgen Antagonists ; administration & dosage ; adverse effects ; therapeutic use ; Bone Density ; drug effects ; Bone Diseases, Metabolic ; etiology ; Calcium ; blood ; urine ; Humans ; Male ; Middle Aged ; Osteoporosis ; etiology ; Parathyroid Hormone ; analysis ; Phosphorus ; urine ; Prostatic Neoplasms ; drug therapy ; metabolism ; Testosterone ; blood