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Eur Urol. 2014 Aug;66(2):232-9. doi: 10.1016/j.eururo.2013.03.055. Epub 2013 Apr 4.

Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade: results from a randomised phase 3 study by the South European Uroncological Group.

Author information

1
Department of Urology, Centro Hospitalar Lisboa Central, Lisbon, Portugal. Electronic address: secretariado@seug-gpgu.org.
2
Department of Urology, Centro Hospitalar Lisboa Central, Lisbon, Portugal.
3
Department of Urology, Klinika Lfuk, Bratislava, Slovakia.
4
Department of Urology, Hospital S. Marcos, Braga, Portugal.
5
Department of Urology, Jessenius School of Medicine, Martin, Slovakia.
6
Department of Urology, Saint James University Hospital, Leeds, UK.
7
Department of Urology, Saint Bartholomew's, London, UK.
8
Department of Urology, Amalia Fleming Hospital, Melissa, Greece.
9
Department of Urology, Policlinico La Rosaleda, Santiago de Compostela, Spain.
10
Department of Mathematics and Statistics, University of Strathclyde, Glasgow, UK; Health Protection Scotland, Glasgow, UK; International Prevention Research Institute, Lyon, France.

Abstract

BACKGROUND:

Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa).

OBJECTIVE:

To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB.

DESIGN, SETTING, AND PARTICIPANTS:

This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa.

INTERVENTION:

During induction, patients received CPA 200 mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25 mg) analogue plus CPA 200 mg/d. Patients whose prostate-specific antigen (PSA) was <4 ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stopped treatment and restarted on CPA 300 mg/d monotherapy if PSA rose to ≥20 ng/ml or they were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRH analogue).

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded.

RESULTS AND LIMITATIONS:

We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treated with IHT reported better sexual function. Among the 462 patients on IHT, 50% and 28% of patients were off therapy for ≥2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy.

CONCLUSIONS:

Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

KEYWORDS:

Intermittent antiandrogen therapy; Maximal androgen blockade; Prostate cancer

PMID:
23582949
DOI:
10.1016/j.eururo.2013.03.055
[Indexed for MEDLINE]

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