Wechsel des LHRH-Analogons beim progredienten kastrationsresistenten Prostatakarzinom

Abstract

Medicinal or surgical castration remains the treatment of choice in metastatic, hormone-naive prostate cancer; however, 2-12% of patients never reach the target serum levels for medicinal castration. We analyzed the therapeutic efficacy of triptorelin pamoate (TP) as salvage treatment due to its higher potency than endogenous luteinizing hormone-releasing hormone (LHRH). The amino acid sequence of TP is identical to that of endogenous LHRH except for position 6 where L-glycine is replaced by D-tryptophane rendering the synthetic moiety less susceptible to cleavage by proteolytic enzymes. In this study 36 patients with prostate-specific antigen (PSA) progression following first line complete androgen blockade and antiandrogen (ADT) withdrawal were retrospectively analyzed. All patients demonstrated no or minimal metastatic disease. The PSA levels, PSA doubling time (PSADT), PSA velocity (PSAV) and testosterone serum concentrations were correlated with the therapeutic response. All patients received TP at a dose of 11.5mg at 3-month intervals until documented progression. The mean patient age was 69.2 years (range 52-79 years), the mean PSA level was 23.4ng/ml (8.7-53.1ng/ml) and the mean PSADT was 9.2 months (2.9-15.4 months). Mean testosterone serum concentration was 38.67ng/dl (21-76ng/dl), the mean time between start of ADT and progression was 42.4 months (13-76 months) and the median time was 46.8 months (16-82 months). A PSA decrease of ≥50% was reached in 9 out of 36 (25%) patients, 3 out of 36 (13.9%) patients each demonstrated stable PSA levels and a prolongation of PSADT from 6.2 to 9.8 months. Mean progression-free survival (PFS) was 21.4 weeks (7-53 weeks). PSA-responders exhibited a PFS of 53.2 weeks (26-64 weeks) as compared to 28 weeks (17-35 weeks) in nonresponders. PSA responders demonstrated significantly higher testosterone serum concentrations of 48.3ng/dl (29-76ng/dl) as compared to nonresponders with 32.6ng/dl (21-62ng/dl, p=0.02). Mean follow-up was 31.4 months (27-39 months), overall survival was 80.5% and cancer-specific survival was 88.9%. Changing the LHRH analogue in castration-refractory prostate cancer (CRPC) with testosterone serum concentrations at or above the castration level results in a temporary PSA response. This treatment option might be included in the therapeutic algorithm of CRPC. Although the PFS is short it allows the continuation of a treatment option with minimal side effects in a mere palliative situation. The data underline the need for continuous monitoring of testosterone during treatment with LHRH analogues.