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Prostate Cancer

Intermittent Versus Continuous Androgen Deprivation Therapy in Patients with Relapsing or Locally Advanced Prostate Cancer: A Phase 3b Randomised Study (ICELAND)

By: Claude Schulmana , Erik Cornelb, Vsevolod Matveevc, Teuvo L. Tammelad, Jan Schramle, Henri Bensadounf, Wolfgang Warnackg, Raj Persadh, Marek Salagierskii, Francisco Gómez Veigaj, Edwina Baskin-Beyk, Beatriz Lópezk and Bertrand Tomball

European Urology, Volume 69 Issue 4, April 2016, Pages 720-727

Published online: 01 April 2016

Keywords: Androgen deprivation, Continuous androgen deprivation, Intermittent androgen deprivation, Prostate cancer, Nonmetastatic, Prostate-specific antigen progression, Testosterone

Abstract Full Text Full Text PDF (492 KB) Patient Summary

Abstract

Background

Intermittent androgen deprivation (IAD) has received increasing attention; however, the current literature is still limited, especially in nonmetastatic prostate cancer (PCa), and the relative efficacy and safety benefits of IAD versus continuous androgen deprivation (CAD) remain unclear.

Objective

To add to the knowledge base regarding efficacy and potential benefits, including reduced side effects and improved quality of life (QoL), of IAD versus CAD in patients with nonmetastatic relapsing or locally advanced PCa.

Design, setting, and participants

A 42-mo phase 3b open-label randomised study in 933 patients from 20 European countries.

Intervention

Following a 6-mo induction with leuprorelin acetate (Eligard) 22.5 mg 3-mo depot, patients were randomised to CAD or IAD with leuprorelin for 36 mo.

Outcome measurements and statistical analysis

The primary end point was time to prostate-specific antigen (PSA) progression while receiving luteinising hormone-releasing hormone agonist, defined as three consecutive increasing PSA values ≥4 ng/ml ≥2 wk apart. Secondary end points included PSA progression-free survival (PFS), overall survival (OS), testosterone levels, performance status, and QoL.

Results and limitations

A total of 933 patients entered the induction phase; 701 were randomised. The median number of injections administered after randomisation was 12 (range: 1−12) for the CAD group and 3 (range: 1–10) for the IAD group. There were no statistically significant or clinically relevant differences between the groups for time to PSA progression, PSA PFS, OS, mean PSA levels over time, or QoL. A similar number of adverse events was observed in each group; the most common were hot flushes and hypertension. Study limitations include the open-label design and absence of formal testosterone recovery assessment.

Conclusions

IAD and CAD demonstrated similar efficacy, tolerability, and QoL in men with nonmetastatic PCa. The principal benefit of IAD compared with CAD is a potential cost reduction with comparable OS rates. There are no apparent QoL benefits.

Patient summary

This randomised trial showed that both intermittent and continuous hormone therapy had similar efficacy, tolerability, and quality-of-life profiles in patients with relapsing M0 or locally advanced prostate cancer. Intermittent therapy may be a valid option for selected patients.

Trial registration

ClinicalTrials.gov identifier NCT00378690.

Take Home Message

Intermittent and continuous hormone therapy demonstrated comparable efficacy, tolerability, and quality of life in patients with relapsing M0 or locally advanced prostate cancer.

Keywords: Androgen deprivation, Continuous androgen deprivation, Intermittent androgen deprivation, Prostate cancer, Nonmetastatic, Prostate-specific antigen progression, Testosterone.

Footnotes

a Clinic E Cavell and University of Brussels, Brussels, Belgium

b Department of Urology, Ziekenhuis Groep Twente, Hengelo, The Netherlands

c Department of Onco-Urology, Cancer Research Centre, Moscow, Russia

d Department of Urology, Tampere University Hospital and Medical School, University of Tampere, Tampere, Finland

e Clinic of Urology and Robotic Surgery, Masaryk's Hospital, Usti nad Labem, Czech Republic

f Department of Urology and Transplantation, Caen University Hospital, Caen, France

g Warnack Private Practice, Hagenow, Germany

h Department of Urology, University Hospitals Bristol NHS Foundation Trust, Bristol, UK

i Second Urology Department, Medical University of Lodz, Lodz, Poland

j A Coruña University Hospital, Urology, A Coruña, Spain, and Urology Department and Kidney Transplant Unit, Salamanca University Hospital, Salamanca, Spain

k Astellas Pharma Global Development, Leiden, The Netherlands

l Institut de Recherche Clinique, Université catholique de Louvain, Brussels, Belgium

Corresponding author. Clinic E Cavell and University of Brussels, Brussels, Belgium. Tel. +32 475 42 36 96.

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