An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer
Adv Ther
An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer
Axel S. Merseburger . Marie C. Hupe 0
0 A. S. Merseburger (&) M. C. Hupe University Hospital Schleswig-Holstein , Lu ̈beck , Germany
Androgen deprivation therapy (ADT) is the mainstay palliative treatment for men with locally advanced and metastatic prostate cancer, and aims to reduce testosterone to levels obtained by surgical castration. Use of gonadotropin-releasing hormone (GnRH) agonists predominates among the ADT options. The GnRH agonist, triptorelin is a first-line hormonal therapy that has demonstrated efficacy and safety in clinical trials of patients with locally advanced non-metastatic or metastatic disease. Sustained-release 1-, 3- and 6-month formulations of triptorelin, administered intramuscularly or subcutaneously, have been developed to provide improved flexibility and convenience for the patient. Head-to-head studies of GnRH agonists are lacking in the field of prostate cancer. Despite the inevitable progression to castration-resistant prostate cancer (CRPC) in most patients receiving ADT, monitoring of testosterone levels needs to improve in routine practice and physicians should not overlook the benefits of continued ADT in their patients when introducing one of the various new treatment options for CRPC. For improved survival outcomes, there remains a need to tailor ADT treatment regimens, novel hormonal agents and chemotherapy according to the individual patient with advanced prostate cancer.
Androgen deprivation therapy; Oncology; Prostate cancer; Sustained-release formulations; Triptorelin
-
INTRODUCTION
Prostate cancer is the most frequently occurring
cancer among European men, with an
estimated incidence of 416,700 (varying from
25 to 193 per 100,000 populations in different
European countries) and an estimated 92,200
deaths in 2012 [1]. In the USA, incidence of
prostate cancer is within this European range at
138 per 100,000 populations according to the
Surveillance, Epidemiology, and End Result
program [2]. Hereditary factors are important
for determining the risk of developing prostate
cancer and exogenous factors may have an
impact on the risk of progression. However, in
general, the risk factors for prostate cancer are
poorly understood and consequent advice on
prevention is not possible [3]. Therefore, the
management of prostate cancer focuses on
treating the disease, and the hormone
dependence of prostate cancer has been
recognized for decades [4]. As a consequence,
testosterone suppression has been the standard
palliative treatment in men with advanced
prostate cancer for many years. Orchiectomy is
a simple, low-cost surgical procedure that
effectively and quickly achieves castration, but
because it is irreversible and does not allow
intermittent treatment, it has become less
popular than hormonal therapies among
patients.
The selection of appropriate treatment is
mainly dependent on the stage of disease and
the risk of progression. Prostate cancer is
generally described as localized, locally
advanced (when the tumor has extended
beyond the capsule of the prostate) and
metastatic disease, and is classified using the
Tumor-lymph Nodes-Metastasis (TNM) system
[5]. Patients are also categorized into low, high,
or intermediate risk of progression according to
clinical stage, Gleason score, and
prostate-specific antigen (PSA) level [6], and
this will continue with the adoption of the
recent International Society of Urological
Pathology (ISUP) modified Gleason grading
patterns [7]. However, a recent assessment of a
large cohort found that while high levels of PSA
([100 ng/ml) at diagnosis were associated with
a reduction in survival after 5 and 10 years,
within this high-risk group PSA level was not
associated with prostate cancer-specific
mortality [8]. Gleason score and the presence
of metastasis were the strongest predictors of
prostate cancer-specific mortality in this group
with high PSA at presentation [8]. What is clear
is that patients classified as having low or
intermediate risk prostate cancer (Gleason
score \8 and PSA \20 ng/ml) may have a
10-year prostate cancer-specific mortality of
\5% [9, 10], and avoiding unnecessary
treatment is a challenge in these patients
[11, 12]. Patients with high-risk prostate
cancer make up a considerable proportion of
newly diagnosed patients and have much
higher mortality rates, and therefore, the
challenge in these men is to increase overall
survival while reducing any adverse effects of
treatment. However, this high-risk population
is heterogeneous and more information is
needed on the validity of suggested prognostic
indicators, such as the number and location of
bone metastases, visceral metastases, Gleason
score, and the initial PSA level [3, 13].
This article reviews the current and ongoing
role of androgen deprivation therapy (ADT) in
the management of prostate cancer, with a
particular focus on clinical trial and rea (...truncated)