Intermittent Versus Continuous Total Androgen Blockade in the Treatment of Patients with Advanced Hormone-Naive Prostate Cancer: Results of a Prospective Randomized Multicenter Trial
De Leval, Jean; Boca, Philippe; Yousef, Eniset al.
2002 • In Clinical Prostate Cancer, 1 (3), p. 163-71
[en] The aim of this study was to compare the efficacy of total intermittent androgen deprivation (IAD) versus total continuous androgen deprivation (CAD) for treating patients with advanced prostate cancer in a phase III randomized trial. A total of 68 evaluable patients with hormone-naive advanced or relapsing prostate cancer were randomized to receive combined androgen blockade according to a continuous (n = 33) or intermittent (n = 35) regimen. Therapeutic monitoring was assessed by use of serum prostate-specific antigen (PSA) measurements. Patients in the CAD and IAD groups were equally stratified for age, biopsy Gleason score, and baseline serum PSA levels. The outcome variable was time to androgen-independence of the tumor, which was defined as increasing serum PSA levels despite androgen blockade. Mean follow-up was 30.8 months. The 35 IAD-treated patients completed 91 cycles, and 19 of them (54.3%) completed > or = 3 cycles. Median cycle length and percentage of time off therapy were 9.0 months and 59.5, respectively. The estimated 3-year progression rate was significantly lower in the IAD group (7.0% +/- 4.8%) than in the CAD group (38.9% +/- 11.2%, P = 0.0052). Our data suggest that IAD treatment may maintain the androgen-dependent state of advanced human prostate cancer, as assessed by PSA measurements, at least as long as CAD treatment. Further studies with longer follow-up times and larger patient cohorts are needed to determine the comparative impacts of CAD and IAD on survival.
Disciplines :
Urology & nephrology
Author, co-author :
De Leval, Jean ; Centre Hospitalier Universitaire de Liège - CHU > Urologie
Boca, Philippe; Centre Hospitalier Régionale de la Citadelle (Liège) - CHR CITADELLE
Yousef, Enis; CHU Sousse Tunisie
Nicolas, Hubert; Centre Hospitalier Régionale de la Citadelle (Liège) - CHR CITADELLE
Jeukenne, Michel; CHU NDB
Seidel, Laurence ; Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique
Bouffioux, Christian ; Université de Liège - ULiège > Département des sciences de la santé publique > Gestion et législation hospitalières
Coppens, Luc ; Centre Hospitalier Universitaire de Liège - CHU > Urologie
Bonnet, Pierre ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie humaine systématique
Andrianne, Robert ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Waltregny, David ; Université de Liège - ULiège > Département des sciences cliniques > Urologie - GIGA-R : Labo de recherche sur les métastases
Language :
English
Title :
Intermittent Versus Continuous Total Androgen Blockade in the Treatment of Patients with Advanced Hormone-Naive Prostate Cancer: Results of a Prospective Randomized Multicenter Trial
Bruchovsky N, Goldenberg L, Gleave M. Intermittent androgen suppression for the treatment of prostate cancer. In: Belldegrun A, Kirby RS, Oliver RT, eds. New Perspectives in Prostate Cancer. Corby, UK: Oxford University Press; 1998:273-282.
Abrahamsson PA. Intermittent androgen suppression. Too good to be true? Scand J Urol Nephrol 1999; 203:45-49.
Bruchovsky N, Klotz LH, Sadar M, et al. Intermittent androgen suppression for prostate cancer: Canadian Prospective Trial and related observations. Mol Urol 2000; 4:191-199.
Akakura K, Bruchovsky N, Goldenberg SL, et al. Effects of intermittent androgen suppression on androgen-dependent tumors. Apoptosis and serum prostate-specific antigen. Cancer 1993; 71:2782-2790.
Noble RL. Sex steroids as a cause of adenocarcinoma of the dorsal prostate in Nb rats, and their influence on the growth of transplants, Oncology 1977; 34:138-141.
Noble RL. Hormonal control of growth and progression in tumors of Nb rats and theory of action. Cancer Res 1977; 37:82-94.
Bruchovsky N, Rennie PS, Coldman AJ, et al. Effects of androgen withdrawal on the stem cell composition of the Shionogi carcinoma. Cancer Res 1990; 50:2275-2282.
Rennie PS, Bruchovsky N, Coldman AJ. Loss of androgen dependence is associated with an increase in tumorigenic stem cells and resistance to cell-death genes. J Steroid Biochem Mol Biol 1990; 37:843-847.
Isaacs JT, Coffey DS. Adaptation versus selection as the mechanism responsible for the relapse of prostatic cancer to androgen ablation therapy as studied in the Dunning R-3327-H adenocarcinoma. Cancer Res 1981; 41:5070-5075.
Isaacs JT, Wake N, Coffey DS, et al. Genetic instability coupled to clonal selection as a mechanism for tumor progression in the Dunning R-3327 rat prostatic adenocarcinoma system. Cancer Res 1982; 42:2353-2371.
Gingrich JR, Barrios RJ, Kattan MW, et al. Androgen-independent prostate cancer progression in the TRAMP model. Cancer Res 1997; 57:4687-4691.
Akakura K, Bruchovsky N, Rennie PS, et al. Effects of intermittent androgen suppression on the stem cell composition and the expression of the TRPM-2 (clusterin) gene in the Shionogi carcinoma. J Steroid Biochem Mol Biol 1996; 59:501-511.
Craft N, Chhor C, Tran C, et al. Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process. Cancer Res 1999; 59:5030-5036.
Sato N, Gleave ME, Bruchovsky N, et al. Intermittent androgen suppression delays progression to androgen-independent regulation of prostate-specific antigen gene in the LNCaP prostate tumour model. J Steroid Biochem Mol Biol 1996; 58:139-146.
Buhler KR, Santucci RA, Royai RA, et al. Intermittent androgen suppression in the LuCaP 23.12 prostate cancer xenograft model. Prostate 2000; 43:63-70.
Trachtenberg J. Experimental treatment of prostatic cancer by intermittent hormonal therapy. J Urol 1987; 137:785-788.
Russo P, Liguori G, Heston WD, et al. Effects of intermittent diethylstilbestrol diphosphate administration on the R3327 rat prostatic carcinoma. Cancer Res 1987; 47:5967-5970.
Klotz LH, Herr HW, Morse MJ, et al. Intermittent endocrine therapy for advanced prostate cancer. Cancer 1986; 58:2546-2550.
Goldenberg SL, Bruchovsky N, Gleave ME, et al. Intermittent androgen suppression in the treatment of prostate cancer: a preliminary report. Urology 1995; 45:839-844.
Higano CS, Ellis W, Russell K, et al. Intermittent androgen suppression with leuprolide and flutamide for prostate cancer: a pilot study. Urology 1996; 48:800-804.
Oliver RT, Williams G, Paris AM, et al. Intermittent androgen deprivation after PSA-complete response as a strategy to reduce induction of hormone-resistant prostate cancer. Urology 1997; 49:79-82.
Grossfeld GD, Small EJ, Carroll PR. Intermittent androgen deprivation for clinically localized prostate cancer: initial experience. Urology 1998; 51:137-144.
Theyer G, Ulsperger E, Baumgartner G, et al. Prolonged response to a single androgen suppression phase in a subpopulation of prostate cancer patients. Ann Oncol 2000; 11:877-881.
Grossfeld GD, Chaudhary UB, Reese DM, et al. Intermittent androgen deprivation: update of cycling characteristics in patients without clinically apparent metastatic prostate cancer. Urology 2001; 58:240-245.
Bouchot O, Lenormand L, Karam G, et al. Intermittent androgen suppression in the treatment of metastatic prostate cancer. Eur Urol 2000; 38:543-549.
Goldenberg SL, Gleave ME, Taylor D, et al. Clinical Experience with Intermittent Androgen Suppression in Prostate Cancer: Minimum of 3 Years' Follow-Up. Mol Urol 1999; 3:287-292.
Evens AM, Lestingi TM, Bitran JD. Intermittent Androgen Suppression as a Treatment for Prostate Cancer: A Review. Oncologist 1998; 3:419-423.
Gleave M, Bruchovsky N, Goldenberg SL, et al. Intermittent androgen suppression for prostate cancer: rationale and clinical experience. Eur Urol 1998; 34:37-41.
Klotz LH, Sogani PC, Block NL. Summary of intermittent endocrine therapy for advanced prostate cancer. Semin Urol Oncol 1997; 15:117-122.
Strum SB, Scholz MC, Strum M. Prolonged non-detectable PSA (NDPSA) in PC patients treated with androgen deprivation may allow for discontinuation of hormone blockade. Presented at International Symposium on Recent Advances in Diagnosis and Treatment of Prostate Cancer, Quebec City, Canada, September 21-23, 1995.
Bruchovsky N, Goldenberg SL, Akakura K, et al. Luteinizing hormone-releasing hormone agonists in prostate cancer. Elimination of flare reaction by pretreatment with cyproterone acetate and low-dose diethylstilbestrol. Cancer 1993; 72:1685-1691.
Strum SB, Scholz MC, McDermed JE. Intermittent androgen deprivation in prostate cancer patients: factors predictive of prolonged time off therapy. Oncologist 2000; 5:45-52.
Crook JM, Szumacher E, Malone S, et al. Intermittent androgen suppression in the management of prostate cancer. Urology 1999; 53:530-534.
Theyer G, Hamilton G. Current status of intermittent androgen suppression in the treatment of prostate cancer. Urology 1998; 52:353-359.
Theyer G, Durer A, Theyer U, et al. Measurements of free and total PSA, tissue polypeptide-specific antigen (TPS), and CYFRA 21-1 in prostate cancer patients under intermittent androgen suppression therapy. Prostate 1999; 41:71-77.
Wolff JM, Tunn UW. Intermittent androgen blockade in prostate cancer: rationale and clinical experience. Eur Urol 2000; 38:365-371.
Oosterlinck W, Mattelaer J, Casselman J, et al. PSA evolution: a prognostic factor during treatment of advanced prostatic carcinoma with total androgen blockade. Data from a Belgian multicentric study of 546 patients. Acta Urol Belg 1997; 65:63-71.
Horwich A, Huddart RA, Gadd J, et al. A pilot study of intermittent androgen deprivation in advanced prostate cancer. Br J Urol 1998; 81:96-99.
Kiratli BJ, Srinivas S, Perkash I, et al. Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer. Urology 2001; 57:127-132.