Less injections by androgen scrutinisation

Chemical or surgical castration is a key strategy in patients with locally
advanced or metastatic prostate cancer. The goal is to eliminate gonadal
testosterone production, so called castration. Currently, both chemical and
surgical castration are considered equal modalities to achieve castration.
Chemical castration is achieved by administering Luteinizing Hormone Releasing
Hormone (LHRH) agonists on a regular basis. However, after prescribing LHRH
agonists, physicians do not monitor the testosterone levels routinely.
Moreover, current dosing regimens are manufacturer-recommended.
Several studies have shown that serum testosterone levels remain longer at or
below castrate levels when 3-monthly depot injections of LHRH agonists are
administered [3 - 7]. This opens opportunities for a personalized way of dosing
LHRH agonists depending on the testosterone level. However, in the performed
testosterone-based dosing studies only the LHRH agonist leuprorelin has been
investigated [3 - 4]. The current study will be initiated to evaluate a
testosterone-based dosing regimen with depot injections of goserelin 10.8 mg
for all eligible patients as well as subgroups of patients.
Based on the performed testosterone-based dosing studies with leuprorelin we
expect that the dosing interval of depot injections of goserelin 10.8 mg can be
prolonged to 5 or 6 months.
An effective personalized treatment regimen will probably lower the treatment
burden (for patients) and treatment costs (for society) while treatment goals
are still achieved.

The primary objective of this study is to determine the possibility to extend
the dosing interval of goserelin 10.8 mg with a testosterone-based dosing
regimen compared to regular treatment with 3-monthly based goserelin 10.8 mg
injections.
This will be achieved by estimating the difference in the number of LHRH
agonist injections in the testosterone based regimen compared to regular
treatment with 3-monthly based goserelin 10.8 mg injections.

The secondary objectives are:
* To determine whether a testosterone-based dosing regimen of goserelin 10.8 mg
is cost-saving compared to regular treatment with a 3-monthly based goserelin
10.8 mg injection.
* To estimate the difference in the time to castrate refractory disease in the
testosterone based regimen compared to regular treatment with 3-monthly based
goserelin 10.8 mg injections.
Collected data will also be used to o develop a pharmacokinetic model for
goserelin in MWPharm.

This study is a randomized, controlled trial. Patients will be randomized to 1)
treatment as usual being 3-monthly depot injections of goserelin 10.8 mg; 2)
treatment with a testosterone-based regimen in a 1:2 fashion.

Control group: Patients treated with regular 3-monthly based goserelin 10.8 mg
injections, regardless of testosterone level.

Study group: Patients will be treated according to the following algorithm.

Algorithm for testosterone-based treatment
Approximately 11 weeks after each depot injection of goserelin 10.8 mg blood
levels of testosterone will be measured. When the following rule applies, a
depot injection of goserelin 10.8 mg is injected subcutaneously into the
anterior abdominal wall at 12 weeks:

A. an increase of more than 0.5 nmol/L from the nadir (the lowest testosterone
achieved during castration)
OR
B. the testosterone level is above 1.2 nmol/L.

When the testosterone level does not meet one of the abovementioned
requirements, goserelin treatment will be postponed, blood levels of
testosterone will be measured again after four weeks (at approx. week 15) and
according to the described algorithm the next depot injection of goserelin 10.8
mg is given or again postponed with 4 weeks. This cycle will continue for every
patient in the study group as long as the testosterone level meets none of the
described requirements.

For the control group, there is no additional risk.

For the study group, study participation not only implies more frequent blood
sampling. It also implies that patients most likely will receive less depot
injections of goserelin 10.8 mg and probably have a lower burden of the
treatment due to the reduction of injections, assuming the testosterone-based
dosing regimen is effective in extending the dosing interval.

The risk for complications due to depot injections of goserelin 10.8 mg and the
risk for side-effects is not affected by this study.