Risks of diabetes mellitus and impaired glucose tolerance induced by intermittent versus continuous androgen-deprivation therapy for advanced prostate cancer / 中华男科学杂志

Objective@#To investigate the correlation of intermittent androgen-deprivation therapy (IADT) and continuous androgen-deprivation therapy (CADT) for advanced prostate cancer (PCa) with the risks of secondary diabetes mellitus (DM) and impaired glucose tolerance (IGT).@*METHODS@#We conducted a retrospective case-control study of the advanced PCa patients treated by IADT or CADT in our hospital from January 2013 to December 2015. Based on the levels fasting blood glucose and 2-hour postprandial blood glucose, results of oral glucose tolerance test, and clinical symptoms of the patients, we statistically analyzed the IADT- or CADT-related risk factors for DM and IGT and the relationship of the body mass index (BMI), hypertension, smoking, and alcohol consumption with secondary DM and IGT.@*RESULTS@#IADT was given to 53 (46.5%) of the patients, aged (69.1 ± 4.3) years, and CADT to 61 (53.5%), aged (70.2 ± 5.7) years. No statistically significant differences were observed in clinical characteristics between the two groups of patients (P > 0.05). BMI, blood pressure, smoking and drinking exhibited no significant influence on the development of DM or IGT either in the IADT (P > 0.05) or the CADT group. The incidence of IGT was significantly lower in the IADT than in the CADT group (P = 0.03), but that of DM showed no statistically significant difference between the two groups (P = 0.64).@*CONCLUSIONS@#Compared with CADT, IADT has a lower risk of IGT and a higher safety in the treatment of advanced prostate cancer.

Comparative study of intermittent versus continuous androgen blockade in the treatment of prostate cancer / 中华泌尿外科杂志

Objective To compare the efficacy and side effects of intermittent androgen depriva-tion (IAD) versus continuous androgen deprivation (CAD) in prostate cancer. Methods Forty-four patients with prostate cancer were divided into 2 groups. Twenty-one cases (group IAD) received IAD therapy. Of them, TNM staging showed T2 in 7 cases, T3 in 9 cases, T4 in 5 cases. The patients were treated by maximum androgen blockage until the serum PSA decreased to less than 0.2 ng/ml and maintained for 2 months. The treatment was resumed when the serum PSA increased up to 10.0 ng/ml or the symptoms occurred progress. Twenty-three cases (group CAD) underwent CAD therapy. Of them, TNM staging showed T2 in 7 cases,T3 in 12 cases,T4 in 4 cases. The time to prostate cancer progression,quality of life and side effect rate were compared between the 2 groups. Results The median time to disease progression was (36±4) months in group IAD and (30±4) months in group CAD,respectively. There was no significant difference between the 2 groups (P=0.132). The mean cycle length was (15.9±2.3) months, among them time on treatment and time off treatment were(8.8±1.5) months and (7.3±0.8) months, respectively. The symptom scores related to treatment in the treatment period and intermission of IAD group were 55.9±16.8 and 47.9±19.7, respective-ly, there was significant difference between them(P=0.007). But the differences between the treat-ment period and intermission in bone pain,urinary and intestinal symptoms were not significant (P> 0.05). The urinary symptom scores after 5 months of continuing treatment in groug CAD was signifi-cantly higher than the basis reference value which was obtained in the sixth month of initial treatment(P=0. 023), but there was no significant changes in the scores of bone pain, intestinal symptoms and symptoms related to treatment(P>0.05). The incidences of hot flash and gynecomastia were 28.6% (6/21) and 19.0%(4/21) in group IAD, 60.9%(14/23) and 52.2%(12/23) in group CAD, respec-tively. There were significant differences between the 2 groups(P<0.05). Conclusions IAD thera-py can alleviate the side effects of androgen deprivation therapy and improve the life quality. The effica-cy of prolonging the time to androgen independence of IAD therapy is similar to CAD therapy.

Factors Predicting the Prolonged Duration of Off-treatment in Intermittent Androgen Deprivation of Prostate Cancer Treatment / 대한비뇨기과학회지

PURPOSE: The goal of intermittent androgen deprivation (IAD) therapy in prostate cancer patients is to delay the disease progression and improve the survival rate. Therefore, the duration of off-treatment is very important for the effective treatment outcome of IAD. We analyzed factors that influence the duration of off-treatment in IAD. MATERIALS AND METHODS: We reviewed the medical records of 45 patients with prostate cancer who had completed at least 1 cycle of IAD. Uni- and multi-variate tests were used to determine the factors, which are predictive to the duration of off-treatment. These factors included: the patient's age, biopsy Gleasons score, initial PSA, presence of bone metastasis, PSA levels at 3 months following on-treatment and at 3 months following off-treatment, and the duration of on-treatment. RESULTS: The average follow up duration was 34 months (15-71 months). The average off-treatment duration of each cycle was 11.1 (4-40), 7.5 (4-14), and 5.6 (3-10) months for the 1st, 2nd and 3rd cycles, respectively. Independent factors associated with the extension of duration of off-treatment, by univariate tests, included: initial PSA value, PSA values at 3 months following on-treatment, PSA at 3 months following off- treatment, and duration of on-treatment. The duration of off-treatment was inversely related to the serum PSA level at the start, 3 months following on-treatment, and 3 months following off-treatment, while it was directly related to the duration of on- treatment by multivariate tests. CONCLUSIONS: The pretreatment serum PSA level and the serum PSA level at 3 months following on-treatment and off-treatment were valuable predictors for the duration of off-treatment in IAD.

Differentiation Related Gene (Drg-1) as a Molecular Marker during the Treatment of in vitro Intermittent Androgen Deprivation in prostate Cancer / 대한비뇨기과학회지

PURPOSE: recent studies have reported that the expression of Drg-1 is up-regulated by androgen. It has been suggested that Drg-1 gene be used as a molecular marker for prostate cancer therapies like PSA. To de termine the role of Drg-1 gene as a molecular marker during intermittent androgen deprivation(IAD) therapy, we investigated the expression of Drg-1 and compared it with PSA expression in human prostate cancer cell lines treated with dihydrotestosterone (DHT) continuously or intermittently. MATERIALS AND METHODS: Two prostate cancer cells having different status of androgen receptor [LNCaP (androgen dependent) and PC-3 (androgen independent)] were used in this study. To know the change in PSA and Drg-1 expression after DHT treatment the cells were cultured in steroid-free RPMI media for 24 hours. 10(-7) and 10(-8)M of DHT and 10(-7)M bicalutimide was added into the cells and then cultured for 72 hours. And we established in vitro IAD model using LNCaP cells. Northern analyses were performed to determine the expression level of both PSA and Drg-1genes. Also, western analyses were performed to determine the protein level of proliferating cellular nuclear antigen and androgen receptor. RESULTS: Transcripts of Drg-1 were detected in both LNCaP and PC-3 cells but PSA was not expressed in PC-3 cells. The expression of Drg-1gene in LNCaP cells was up-regulated by 10(-8)M of DHT like PSA gene and down-regulated by 10(-7)M bicalutamide. In the treatment of intermittent androgen deprivation, the expression pattern of Drg-1was similar to that of PSA. However, up-regulation of PSA was detected earlier than of Drg-1. CONCLUSIONS: Based on observation, Drg-1 was up-regulated by androgen and down-regulated by anti-androgen. This suggests that Drg-1gene is useful for determining the androgen independency of prostate cancer during IAD.

Intermittent Androgen Deprivation with Goserelin and Flutamide for Prostate Cancer: a Pilot Study / 대한비뇨기과학회지

PURPOSE: The purpose of this study was to evaluate the feasibility of using intermittent androgen deprivation(IAD) in patients with prostate cancer. MATERIALS AND METHODS: We reviewed the medical records of 29 patients treated with IAD for prostate cancer. Androgen deprivation with goserelin and flutamide was continued for at least 4 months after serum prostate specific antigen(PSA) became undetectable or a nadir level was reached. Medication was then discontinued until serum PSA reached a predetermined level. This cycle of treatment was repeated until there was evidence of androgen independence. RESULTS: Twenty-one patients completed the on-treatment during cycle 1, with a median time to PSA nadir of 3 months. Nine patients completed cycle 1 with a median time of off-treatment of 11 months(38% of a treatment cycle). Eight patients continued the off-treatment during cycle 1 for 1+ to 8+ months. During cycle 2, 3 patients achieved a PSA nadir in a median time of 3.5 months. While off treatment, most patients reported reduction of symptoms associated with androgen suppression. CONCLUSIONS: IAD is a feasible alternative for continuous androgen deprivation for treatment of prostate cancer. It also results in the reducion of toxicity, cost of treatment, and possibly a delay in tumor progression.