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This study was conducted with the aim to investigate the feasibility of intermittent treatment with docetaxel chemotherapy for castration-resistant prostate cancer (CRPC). A total of 51 men with CRPC received docetaxel at 75 mg/m2 every 3 weeks combined with oral dexamethasone 1.0-2.0 mg/day between 2008 and 2013. The prostate-specific antigen (PSA) level was monitored every 3 weeks. Chemotherapy was suspended when the serum PSA level decreased to <4 ng/ml, with a reduction rate of >50% from the baseline. Treatment was resumed when serum PSA increased to >2 ng/ml, with an increase rate of >50% from the nadir. Of the 51 cases, 27 (52.9%) qualified for intermittent treatment; 17 patients received two courses of docetaxel chemotherapy and 10 received three courses. The median off-treatment interval was 266 days for the first drug holiday, 129.5 days for the second and 146.5 days for the third. The multivariate analysis indicated low baseline PSA (

Use of intermittent androgen-deprivation therapy ( IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side-effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first-line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high-risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short- and long-term side-effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side-effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT-related side-effects, and, to a degree, their impact on patient health-related quality of life ( HRQL). Further comparative study is required, particularly in relation to HRQL and long-term complications associated with ADT. [ABSTRACT FROM AUTHOR]

Abstract: Context: Intermittent androgen deprivation (IAD) in prostate cancer (PCa) patients has been proposed to delay development of castration resistance and to reduce the side effects and costs of androgen deprivation therapy (ADT). Objective: This review analyzes (1) the oncologic and quality of life (QoL) results from randomized phase 3 trials comparing IAD and continuous ADT and (2) the prognostic parameters for IAD. Evidence acquisition: We searched the Medline and Cochrane Library databases (primary fields: prostate neoplasm and intermittent androgen deprivation; secondary fields: randomized trials, survival, quality of life, predictors) without language restriction. Evidence synthesis: We found seven extensively described phase 3 trials randomizing 4675 patients to IAD versus continuous ADT. Other randomized trials investigating IAD have been performed, but available data are limited and have been published only in preliminary fashion. In all seven trials, patients spent most of their time on, rather than off, ADT. The induction periods ranged from 3 mo to 8 mo; in all but one trial, the PSA level designated for ADT discontinuation was <4 ng/ml. Mean follow-up ranged from 40–108 mo. Collectively, these trials support the concept that, mainly in metastatic cases, IAD can produce oncologic results similar to continuous ADT. In terms of overall survival, the hazard ratios for IAD and continuous ADT were very similar (range: 0.98–1.08). The QoL benefit of IAD appears to be modest at best. With IAD, QoL is likely influenced by the duration of the off-treatment periods and by the rate of testosterone recovery. Conclusions: The evidence indicates that IAD is not inferior to continuous ADT. Data are insufficient to determine whether IAD is able to prevent the long-term complications of ADT. More comparative analysis focused on QoL is warranted. [Copyright &y& Elsevier]

Abstract: Context: Androgen-deprivation therapy (ADT) is the mainstay of treatment for metastatic prostate cancer and is also recommended in association with external-beam radiation therapy (EBRT) for patients with high-risk disease. Objective: Our aim was to make recommendations regarding optimal timing of ADT, target serum testosterone levels, intermittent ADT delivery, and quality of life (QoL) during ADT. Evidence acquisition: This review contains recommendations from a European expert panel held in May 2009. Evidence synthesis: There is ongoing debate over whether ADT should be initiated at diagnosis or delayed until biochemical or symptomatic progression. Immediate ADT is recommended for metastatic disease to defer symptom development and reduce serious complications. In node-positive disease or high-risk nonmetastatic disease unfit for curative therapy, immediate ADT is also an option. Furthermore, there is a clear benefit of adjuvant ADT in association with EBRT in patients with high-risk disease. Some retrospective evidence also supports adjuvant ADT use following radical prostatectomy for high-risk localised disease. In cases of biochemical relapse after definitive local therapy, early ADT may benefit patients with poor prognostic factors. For patients on ADT, the traditional <50ng/dl target for serum testosterone levels should be considered outdated. It is now clear that a <20ng/dl threshold better reflects the outcome of bilateral orchidectomy, which is considered the standard of reference in ADT. Recent data demonstrate a clinical benefit of testosterone reduction to more stringent targets than the historical <50ng/dl threshold. In addition, emerging evidence suggests that intermittent scheduling of ADT can reduce adverse events and improve QoL without compromising survival, but further data are needed to guide its clinical use. Finally, adverse events of ADT may affect QoL and must be discussed with patients. Conclusions: Based on current evidence, the panel made several recommendations for the clinical implementation of ADT. [Copyright &y& Elsevier]

To present oncological results with intermittent androgen deprivation (IAD) in a single center. Between 1992 and 2008, 566 patients with prostate cancer (PC) were selected for a non-randomized study of IAD. Two hundred and eighteen patients had biochemical recurrence (BCR) after local treatment for PC and 348 patients had micro- or macro-metastatic disease. On-treatment period (ONTP) consisted of three-monthly injections of gonadatropin-releasing hormone (GnRH) agonist combined with daily oral androgen receptor antagonist. Off-treatment period (OFTP) was indicated when prostate-specific antigen (PSA) was <4 ng/ml. Criteria for resumption of hormonal therapy were PSA >20 ng/ml or clinical symptoms. Cancer specific survival curves were computed according to the Kaplan–Meier method. Median follow-up was 81 months (12–230). Median age was 74.7 years (52–92). Median Gleason score at diagnosis was 7 (3–9). Median initial PSA was 17 ng/ml (0.4–433). Cycle duration decreased progressively from 23 months for the 1st cycle to 10 months at 12th cycle. The number of patients who became hormone resistant was 182 (32%). Median cancer specific survival probability for the series is 12 (10.8–infinity) years. No previous treatment group showed a higher cancer specific survival probability (log rank test, CI 95%, P = 0.003) versus BCR group. Multivariate analysis of cancer specific survival demonstrates age, initial Gleason score and initial PSA level as significant factors affecting mortality ( P < 0.05). Intermittent androgen deprivation is an acceptable treatment in different stages of PC. Duration of cycle decreased progressively during therapy. Age, Gleason score and PSA are factors predicting mortality. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate, over a 10-year period, the feasibility, efficacy, duration of action and adverse effects of intermittent hormonal therapy (IHT) in patients with advanced prostate cancer or biochemical recurrence after radical treatment.Materials and Methods: Two hundred and thirty-three patients with prostate cancer have been included in an IHT protocol since 1992. Fifty-five patients had already been treated by radical prostatectomy (group A), 35 patients had received radiotherapy or a treatment with high-intensity focused ultrasound (HIFU) (group B) and 143 patients had not received any previous treatment (group C). Three-monthly injection of LHRH analogue combined with a non-steroidal antiandrogen was administered during the treatment phase (“on” phase). Treatment was stopped (“off” phase) when the PSA level fell below 4 ng/ml, regardless of the duration of the “on” phase. Criteria for resumption of hormonal therapy were PSA >20 ng/ml, PSA progression slope over the previous three months >5 ng/ml per month or recurrence of pain or urinary symptoms.Results: The median follow-up was 34.9 months (range: 13–151) and the median initial PSA was 28 ng/ml (range: 1–433). Five cycles were performed in the patients with the longest follow-up. The mean duration of cycles was gradually decreased from 19.6 months to 11.8 months. The “on/off” ratio was close to 30% regardless of the cycle or patient group. Ten patients (4%) died from their cancer during the study, with a median survival of 42.2 months. Six patients (2.5%) developed painful symptoms during IHT.Conclusions: IHT ensures medium-term (three years) control of the disease, using a treatment resumption criteria of PSA >20 ng/ml and was not associated with major complications. [Copyright &y& Elsevier]