Der Urologe

, Volume 51, Issue 9, pp 1282–1287 | Cite as

Wechsel des LHRH-Analogons beim progredienten kastrationsresistenten Prostatakarzinom

  • A. Heidenreich
  • D. Porres
  • R. Epplen
  • T. van Erps
  • D. Pfister
Originalien

Zusammenfassung

Hintergrund

Standardtherapie des metastasierten Prostatakarzinoms (PCA) ist die medikamentöse oder chirurgische Kastration – 2–12% der Patienten erreichen dieses Ziel nach medikamentöser Kastration jedoch nicht. Wir untersuchten, ob ein Wechsel des primären LHRH-Analogons (Luteinisierungs-Hormon-Releasing-Hormon) auf Triptorelinpamoat (TP) zu einem erneuten therapeutischen Ansprechen führen kann.

Patienten und Methodik

Retrospektiv wurden 36 Patienten mit einem PSA-Progress von ≥50% gegenüber dem Nadir nach kompletter Androgendeprivation (ADT) und sekundärem Antiandrogenentzug analysiert. Alle Patienten zeigten nach bildgebender Standarddiagnostik keine oder nur minimale Metastasen und waren symptomfrei. Es wurden prätherapeutisch die Parameter PSA (prostataspezifisches Antigen), PSA-Verdopplungszeit (PSA-DT), PSA-Velocity (PSA-V) sowie die Testosteronserumkonzentration (TK) bestimmt und mit der beobachteten Ansprechrate korreliert. Alle Patienten wurden mit TP, 11,5 mg in 3-monatlichen Intervallen bis zum Progress therapiert.

Ergebnisse

Das mittlere Patientenalter lag bei 69,2 (52–79) Jahren, der mittlere PSA-Wert bei 23,4 (8,7–53,1) ng/ml, Die mittlere PSA-DT betrug 9,2 (2,9–15,4) Monate. Die mittlere Testosteronkonzentration betrug 38,67 (21–76) ng/dl. Die mittlere Zeit der ADT bis zur dokumentierten PSA-Progression betrug 42,4 (13–76) Monate, die mediane Zeit lag bei 46,8 (16–82) Monaten. Eine PSA-Reduktion ≥ 50% wurde bei 9/36 (25%) Patienten nachgewiesen. Jeweils 3/36 (13,9%) Patienten zeigten stabile PSA-Werte bzw. eine reduzierte PSA-DT (6,2→9,8 Monate). Das mittlere progressionsfreie Intervall (PFI) lag bei 21,4 (7–53) Wochen. Bei PSA-Ansprechen betrug das mittlere PFI 53,2 (26–64) Wochen, bei stabilem PSA-Verlauf 28 (17–35) Wochen. Patienten mit signifikanter PSA-Regression wiesen signifikant höhere TK auf als Patienten ohne PSA-Antwort (48,3 (29–76) ng/dl vs. 32,6 (21–62) ng/dl, p=0,02). Das mittlere Nachbeobachtungsintervall beträgt 31,4 (27–39) Monate. Die Gesamtüberlebensrate 80,5%, die tumorspezifische Überlebensrate beträgt 88,9%.

Zusammenfassung

Die sekundäre LHRH-Gabe führt bei kastrationsresistenten Prostatakarzinomen (KRPCA) und begleitender T-Konzentration im hohen Kastrationsniveau zu einem vorübergehenden therapeutischen Ansprechen und kann in das Therapiekonzept bei vermeintlicher „Kastrationsresistenz“ berücksichtigt werden. Unsere Daten verdeutlichen die Bedeutung der Bestimmung der T-Konzentration unter LHRH-Therapie. Auch wenn das progressionsfreie Intervall kurz ist, erlaubt es die Fortesetzung einer nebenwirkungsarmen Therapie in einer reinen palliativen Situation.

Schlüsselwörter

Prostatakarzinom, kastrationsresistentes LHRH-Analoga Triptorelin Pamoate Degarelix Chemotherapie 

Change of the LHRH analogue in progressive castration-refractory prostate cancer

Abstract

Introduction

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.

Patients and Methods

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 11.5 mg at 3-month intervals until documented progression.

Results

The mean patient age was 69.2 years (range 52-79 years), the mean PSA level was 23.4 ng/ml (8.7-53.1 ng/ml) and the mean PSADT was 9.2 months (2.9–15.4 months). Mean testosterone serum concentration was 38.67 ng/dl (21–76 ng/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 48.3 ng/dl (29–76 ng/dl) as compared to nonresponders with 32.6 ng/dl (21–62 ng/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%.

Conclusion

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.

Keywords

Prostate cancer, castration-resistant LHRH analogues Triptorelin pamoate Degarelix Chemotherapy 

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • A. Heidenreich
    • 1
  • D. Porres
    • 1
  • R. Epplen
    • 1
  • T. van Erps
    • 1
  • D. Pfister
    • 1
  1. 1.Klinik und Poliklinik für UrologieUniversitätsklinikum AachenAachenDeutschland

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