Randomised prospective study of intermittent versus continuous androgen suppression in advanced prostate cancer

Abstract

5015 Background: Based on results of animal experiments intermittent androgen blockade was suggested to delay progression of advanced prostate cancer to the hormone refractory stage. We conducted a prospective randomized study to compare intermittent with continuous androgen suppression. Methods: This was a multi-centre, randomised, two-arm study comparing treatment with goserelin + bicalutamide (intermittent, group A) vs. goserelin + bicalutamide (continuous, group B). The primary endpoint was time to clinical and/or biochemical progression of the disease despite androgen suppression. Secondary enpoints were survival time, patient’s quality of life (QoL) and toxicity. Patients eligibility criteria were: histologically confirmed adenocarcinoma of the prostate in clinical stage T1–4N1–3M0 or T1–4N0–3M1 (D1 oder D2). After an induction phase of 24 weeks with MAB, 335 patients whose PSA decreased under 4 ng/ml or = 90% from baseline were randomized. Results: About two-thirds of the patients of both the intermittent and the continuous therapy arm (65% versus 66%, ITT population) experienced a clinical and/or biochemical disease progression due to any reason during this study. The median time to disease progression was longer for patients randomised to the intermittent therapy arm (16.6 months) compared with patients randomised to the continuous therapy arm (11.5 months). This difference however was not statistically significant (log rank test, p=0.1758). The median time to death from any cause was 51.4 month in the intermittent arm compared and 53.8 months in the continuous therapy arm (p = 0.658). There were no differences in the incidence of patients with AEs or SAEs or in any other safety parameter between patients treated intermittently and patients treated continuously. Patients’ self-assessment of their overall health and of their sexual activity appeared to be favourable in the intermittent compared with the continuous therapy arm. 88% of all patients treated intermittently experienced more than 50% of the number of treatment days as treatment-free days. Conclusions: Intermittent therapy in D1 and D2 prostate cancer patients appears to be safe and feasible. Off treatment periods are > 40 % and attribute to patients quality of life. No significant financial relationships to disclose.

Safety and tolerability of intermittent androgen deprivation therapy: A literature review

“…We identified and reviewed publications from 25 IAD studies; of these, 13 were selected for the present literature review based on their relevance to assess safety and tolerability of IAD (Tables 2,3). Of these 13 studies, eight were randomized , active-controlled studies comparing IAD with CAD (Table 2; n = 68 to 1386 patients), 28,29,[31][32][33][34][35][36][37][38][39] and five were observational, non-randomized studies ( Table 3; n = 19 to 250 patients). 9,[40][41][42][43] Of these eight active-controlled studies, two 31,32 were published in full, whereas preliminary results have been reported in abstract format for the remaining six studies.…”

“…9,[40][41][42][43] Of these eight active-controlled studies, two 31,32 were published in full, whereas preliminary results have been reported in abstract format for the remaining six studies. 29,33,[35][36][37][38]…”

“…Improved sexual dysfunction was observed in six of the 13 studies. 32,35,40,42,43,45 In 2002, de Leval reported that the loss of libido and erectile dysfunction, which occurred during CAD, was improved during IAD. 32 Similar observations were reported by Malone et al, who noted that libido and erection were generally lost during the on-treatment periods of IAD; however, 47% of patients were able to regain sexual function in the off-treatment periods, and this correlated with testosterone level normalization.…”

Hormonal therapy for prostate cancer: Current topics and future perspectives

“…Several randomized comparative clinical trials have been conducted to compare the efficacy between intermittent and continuous androgen suppression (Table 3). [27][28][29][30][31][32][33][34] At the present time, while only a few trials have obtained the final results, 27 no report has demonstrated a significantly worse time to progression and survival with intermittent androgen suppression than with continuous androgen suppression. On the other hand , most trials have indicated that the benefits of intermittent therapy were fewer adverse effects and increased quality of life.…”

“…Randomized control trials comparing intermittent vs continuous androgen suppression[27][28][29][30][31][32][33][34] …”