THE "NEW" PROSTATE CANCER INFOLINK

Before the coming of the PSA test, urologists used to use serum acid phosphatase levels (usually) and serum alkaline phosphatase (S-ALP) levels (less commonly) to assess the status of men at risk for or under treatment for metastatic prostate cancer.

In the pivotal phase III trial of the “second-generation” LHRH antagonist degarelix (Firmagon), the developers monitored S-ALP levels in all patients involved in the trial, whether they were receiving degarelix or the comparator product (leuprolide acetate, and LHRH agonist in a 7.5 mg monthly depot formulation).

In a recent paper, Schröder et al. report data on the S-ALP levels of men who received the approved dose of degarelix (an initial loading dose of 240 mg followed by monthly doses of 80 mg) compared to the S-ALP levels of men receiving leupolide acetate.

The results of their analysis show that:

• Patients had a median age of 73 years and a median PSA level of 19.0 ng/ml.
• Baseline S-ALP levels were high in metastatic patients and highest in patients with metastatic disease and a haemoglobin level of <13 g/dl.
• In patients with metastatic disease, after initial peaks in both patient groups, S-ALP levels were suppressed below baseline with degarelix but were maintained at about baseline levels with leuprolide.
• The late rise in S-ALP seen with leuprolide was not apparent with degarelix.
•  The pattern of S-ALP response was similar in patients with a baseline PSA level of ≥ 50 ng/ml.
• Between-treatment differences in patients with metastatic disease and those with a PSA level of ≥ 50 ng/ml were significant at day 364
• Patients with metastatic disease or those with PSA levels of ≥ 50 ng/ml at baseline had greater reductions in S-ALP levels with degarelix than with leuprolide.

Apparently patients in the degarelix group maintained S-ALP suppression better, throughout the study, than the patients in the leuprolide group. The authors speculate that degarelix might offer better S-ALP control than leuprolide and go on to state that degarelix “might prolong control of skeletal metastases, compared with [LHRH] agonists, over a 1-year treatment period.”

If degarelix is actually capable of superior control of the development of skeletal metastases over time, compared to the LHRH agonists like leuprolide, then this implies the possibility that hormone therapy with degarelix also offers a time to disease progression and/or a long-term survival benefit compared to the LHRH agonists. It is not entirely clear, however, whether the current trials of degarelix will be sufficiently powerful to identify such clinical effects.

It is worth remembering that the 7.3-month survival benefit claimed 20 years ago for the addition of the antiandrogen flutamide to leuprolide acetate (maximal androgen deprivation or combined androgen blockade) has long been much disputed. Treatment with degarelix is comparable to combined androgen blockade, but whether it can show a survival benefit compared to treatment with an LHRH agonist alone might be very difficult to prove today because of the many other drugs now shown to have meaningful activity in second- and third-line therapy after failure of first-line hormone therapy.

Filed under: Living with Prostate Cancer, Management | Tagged: Degarelix, serum alkaline phosphatase