Intermittent versus continuous androgen suppression for prostatic cancer.

BACKGROUND After lung cancer, prostate cancer is the most common cause of death among males. The aim of treatment is to prevent disease-related morbidity and mortality while minimizing intervention-related adverse events. Androgen suppression therapy (AST) to reduce circulating serum testosterone and disease progression is considered a mainstay of treatment for men with advanced prostate cancer. It has been increasingly utilized for early stage disease despite a lack of evidence of effectiveness. OBJECTIVES Evaluate the effectiveness and safety of intermittent androgen suppression (IAS) compared to continuous androgen suppression for treating prostatic cancer. SEARCH STRATEGY The following databases were searched to identify randomised or quasi-randomised, controlled trials comparing intermittent and continuous androgen suppression in the treatment of any stage of prostate cancer: the Cochrane Central Register of Controlled Trials; EMBASE and LILACS. SELECTION CRITERIA Studies were included if they were randomised or quasi-randomized, and compare the effects of IAS versus CAS. DATA COLLECTION AND ANALYSIS Two reviewers selected relevant trials, assessed methodological quality and extracted data. MAIN RESULTS Five randomized studies involving 1382 patients were included in this review. All the included studies involved advanced (T3 or T4) prostate cancer, had relatively small populations, and were of short duration. Few events were reported and did not assess disease-specific survival or metastatic disease. Only one study (N = 77) evaluated biochemical outcomes. A subgroup analysis found no significant differences in biochemical progression (defined by the authors as PSA >/= 10 ng/mL) between IAS and CAS for Gleason scores 4 - 6, 7, and 8 - 10. For patients with a Gleason score > 6, reduction in biochemical progression favoured the IAS group (RR 0.10, 95% CI 0.01 to 0.67, P = 0.02). Studies primarily reported on adverse events. One trial (N = 43) found no difference in adverse effects (gastrointestinal, gynecomastia and asthenia) between IAS ( two events) and CAS (five events), with the exception of impotence, which was significantly lower in the IAS group (RR 0.72, 95% CI 0.56 to 0.92, P = 0.008). AUTHORS' CONCLUSIONS Data from RCTs comparing IAS to CAS are limited by small sample size and short duration. There are no data for the relative effectiveness of IAS versus CAS for overall survival, prostate cancer-specific survival, or disease progression. Limited information suggests IAS may have slightly reduced adverse events. Overall, IAS was also as effective as CAS for potency, but was superior during the interval of cycles (96%).

[1]  C. Tangen,et al.  Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  L. Klotz,et al.  The relationship between the androgen receptor CAG repeat polymorphism length and the response to intermittent androgen suppression therapy for advanced prostate cancer , 2005, Prostate Cancer and Prostatic Diseases.

[3]  S. Steinberg,et al.  A prospective analysis of the time to normalization of serum androgens following 6 months of androgen deprivation therapy in patients on a randomized phase III clinical trial using limited hormonal therapy. , 2005, The Journal of urology.

[4]  Y. Ohashi,et al.  Effectiveness of adjuvant intermittent endocrine therapy following neoadjuvant endocrine therapy and external beam radiation therapy in men with locally advanced prostate cancer , 2005, The Prostate.

[5]  A. Bono,et al.  Phase III study of intermittent MAB versus continuous MAB international cooperative study , 2005 .

[6]  N. Sato,et al.  Intermittent androgen suppression for locally advanced and metastatic prostate cancer: preliminary report of a prospective multicenter study. , 2004, Urology.

[7]  J. Hines,et al.  Long-Term Outcomes in Patients with Prostate Cancer Managed with Intermittent Androgen Suppression , 2004, Urologia Internationalis.

[8]  A. De la taille,et al.  Intermittent androgen suppression in patients with prostate cancer , 2003, BJU international.

[9]  P. Bonnet,et al.  Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naive prostate cancer: results of a prospective randomized multicenter trial. , 2002, Clinical prostate cancer.

[10]  F. Labrie,et al.  Can combined androgen blockade provide long-term control or possible cure of localized prostate cancer? , 2002, Urology.

[11]  H. Nicolas,et al.  Intermittent versus continuous total androgen blockade in the treatment of patients with advanced hormone-naïve prostate cancer. Results of a randomiszed prospective multicenter clinical trial , 2002 .

[12]  P. Carroll,et al.  Intermittent androgen deprivation: update of cycling characteristics in patients without clinically apparent metastatic prostate cancer. , 2001, Urology.

[13]  A. Sciarra,et al.  Intermittent androgen deprivation (IAD) in patients with biochemical failure after radical retropubic prostatectomy (RRP) for clinically localized prostate cancer , 2000, World Journal of Urology.

[14]  L. Lenormand,et al.  Intermittent Androgen Suppression in the Treatment of Metastatic Prostate Cancer , 2000, European Urology.

[15]  M. Scholz,et al.  Intermittent androgen deprivation in prostate cancer patients: factors predictive of prolonged time off therapy. , 2000, The oncologist.

[16]  M. Srougi,et al.  METASTATIC ADENOCARCINOMA OF THE PROSTATE: COMPARISON BETWEEN CONTINUOUS AND INTERMITTENT HORMONAL TREATMENT , 2000 .

[17]  C. Carneiro,et al.  Phase III study on intermittent MAB vs continuous MAB: an international co-operative study , 1999, Prostate Cancer and Prostatic Diseases.

[18]  N. Mottet,et al.  Intermittent versus continuous hormone deprivation in metastatic prostate cancer: preliminary data from an ongoing European study , 1999, Prostate Cancer and Prostatic Diseases.

[19]  J. Crook,et al.  Intermittent androgen suppression in the management of prostate cancer. , 1999, Urology.

[20]  Goldenberg,et al.  Clinical Experience with Intermittent Androgen Suppression in Prostate Cancer: Minimum of 3 Years' Follow-Up. , 1999, Molecular urology.

[21]  J. Rambeaud Intermittent Complete Androgen Blockade in Metastatic Prostate Cancer , 1998, European Urology.

[22]  U. Tunn,et al.  Intermittent Complete Androgen Blockade in PSA Relapse after Radical Prostatectomy and Incidental Prostate Cancer , 1998, European Urology.

[23]  G. Theyer,et al.  Current status of intermittent androgen suppression in the treatment of prostate cancer. , 1998, Urology.

[24]  G. Andriole,et al.  A phase I/II dose ranging study of DUROS (TM) (leuprolide) implantable therapeutic system in patients with advanced prostate cancer , 1998 .

[25]  Kurek,et al.  Intermittent Complete Androgen Blockade in PSA Relapse after Radical Prostatectomy and Incidental Prostate Cancer. , 1998, European urology.

[26]  P. Carroll,et al.  Intermittent androgen deprivation for clinically localized prostate cancer: initial experience. , 1998, Urology.

[27]  D. Dearnaley,et al.  A pilot study of intermittent androgen deprivation in advanced prostate cancer. , 1998, British journal of urology.

[28]  Á. Atallah,et al.  Optimal search strategy for clinical trials in the Latin American and Caribbean Health Science Literature Database (LILACS). , 1997, Sao Paulo medical journal = Revista paulista de medicina.

[29]  G. Williams,et al.  Intermittent androgen deprivation after PSA-complete response as a strategy to reduce induction of hormone-resistant prostate cancer. , 1997, Urology.

[30]  D G Altman,et al.  Statistics Notes: Detecting skewness from summary information , 1996, BMJ.

[31]  W. Ellis,et al.  Intermittent androgen suppression with leuprolide and flutamide for prostate cancer: a pilot study. , 1996, Urology.

[32]  R L Vessella,et al.  Cell proliferation and apoptosis during prostatic tumor xenograft involution and regrowth after castration , 1996, International journal of cancer.

[33]  A R Jadad,et al.  Assessing the quality of reports of randomized clinical trials: is blinding necessary? , 1996, Controlled clinical trials.

[34]  M. Gleave,et al.  Intermittent androgen suppression in the treatment of prostate cancer: a preliminary report. , 1995, Urology.

[35]  M. Clarke,et al.  Identifying relevant studies for systematic reviews , 1995, BMJ.

[36]  K. Dickersin,et al.  Systematic Reviews: Identifying relevant studies for systematic reviews , 1994 .

[37]  S. Goldenberg,et al.  Effects of intermittent androgen suppression on androgen‐dependent tumors. Apoptosis and serum prostate‐specific antigen , 1993, Cancer.

[38]  A. Coldman,et al.  Loss of androgen dependence is associated with an increase in tumorigenic stem cells and resistance to cell-death genes , 1990, The Journal of Steroid Biochemistry and Molecular Biology.

[39]  U. Storb The Published Data , 1990, Immunological reviews.

[40]  A. Coldman,et al.  Effects of androgen withdrawal on the stem cell composition of the Shionogi carcinoma. , 1990, Cancer research.

[41]  L. Klotz,et al.  Intermittent endocrine therapy for advanced prostate cancer , 1986, Cancer.

[42]  C. Huggins,et al.  STUDIES ON PROSTATIC CANCER: II. THE EFFECTS OF CASTRATION ON ADVANCED CARCINOMA OF THE PROSTATE GLAND , 1941 .