In an open-label, noncomparative, multicenter clinical study of LUPRON DEPOT 30 mg for 4-month administration, 49 patients with stage D2 prostatic adenocarcinoma (with no prior treatment) were enrolled. The objectives were to determine whether a 30 mg depot formulation of leuprolide injected once every 16 weeks would reduce and maintain serum testosterone levels at castrate levels (≤ 50 ng/dL), and to assess the safety of the formulation. The study was divided into an initial 32-week treatment phase and a long-term treatment phase. Serum testosterone levels were determined biweekly or weekly during the first 32 weeks of treatment. Once the patient completed the initial 32-week treatment period, treatment continued at the investigator’s discretion with serum testosterone levels being done every 4 months prior to the injection. 

In the majority of patients, testosterone levels increased 50% or more above the baseline during the first week of treatment. Mean serum testosterone subsequently suppressed to castrate levels within 30 days of the first injection in 94% of patients and within 43 days in all 49 patients during the initial 32-week treatment period. The median dosing interval between injections was 112 days. One escape from suppression (two consecutive testosterone values greater than 50 ng/dL after castrate levels achieved) was noted at Week 16. In this patient, serum testosterone increased to above the castrate range following the second depot injection (Week 16) but returned to the castrate level by Week 18. No adverse reactions were associated with this rise in serum testosterone. A second patient had a rise in testosterone at Week 17, then returned to the castrate level by Week 18 and remained there through Week 32. In the long-term treatment phase two patients experienced testosterone elevations, both at Week 48. Testosterone for one patient returned to the castrate range at Week 52, and one patient discontinued the study at Week 48 due to disease progression. 

Secondary efficacy endpoints evaluated in the study were the objective tumor response as assessed by clinical evaluations of tumor burden (complete response, partial response, objectively stable and progression) and evaluations of changes in prostatic involvement and prostate-specific antigen (PSA). These evaluations were performed at Weeks 16 and 32 of the treatment phase. The long-term treatment phase monitored PSA at each visit (every 16 weeks). The objective tumor response analysis showed “no progression” (i.e. complete or partial response, or stable disease) in 86% (37/43) of patients at Week 16, and in 77% (37/48) of patients at Week 32. Local disease improved or remained stable in all patients evaluated at Week 16 and/or 32. For patients with elevated baseline PSA, 50% (23/46) had a normal PSA (less than 4.0 ng/mL) at Week 16, and 51% (19/37) had a normal PSA at Week 32. 

Periodic monitoring of serum testosterone and PSA levels is recommended, especially if the anticipated clinical or biochemical response to treatment has not been achieved. It should be noted that results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions. 

Using historical comparisons, the safety and efficacy of LUPRON DEPOT 30 mg for 4-month administration appear similar to the other LUPRON DEPOT formulations. 

Figure 10. LUPRON DEPOT 30 mg for 4-Month Administration Mean Serum Testosterone Concentrations