ABSTRACT
Luteinizing hormone杛eleasing hormone agonist (LHRH?A), goserelin, and antagonist, degarelix, are both indicated for the treatment of advanced prostate cancer (PCa); however, large comparative trials evaluating their efficacy and safety are lacking. In this review, we assessed the available evidence for both the drugs. Although degarelix achieves an early rapid decline in testosterone (T) and prostate?specific antigen (PSA) levels, median T and PSA levels, in addition to prostate volume and International Prostate Symptom Scores, become comparable with goserelin over the remaining treatment period. Degarelix causes no initial flare, therefore it is recommended in patients with spinal metastases or ureteric obstruction. Goserelin achieves lower PSA, improved time to progression, and better survival outcomes when administered adjunctively to radiotherapy compared with radiotherapy alone, with significant results even over long?term follow?up. The evidence supporting adjuvant degarelix use is limited. Goserelin has better injection site safety, single?step delivery, and an efficient administration schedule compared with degarelix, which has significantly higher injection site reactions and less efficient administration mechanism. There is conflicting evidence about the risk of cardiovascular disease (CVD), and caution is required when using LHRH?A in patients with preexisting CVD. There is considerable long?term evidence for goserelin in patients with advanced PCa, with degarelix being a more recent option. The available comparative evidence of goserelin versus degarelix has several inherent limitations related to study design, sample size, conduct, and statistical analyses, and hence warrants robust prospective trials and long?term follow?up.
ABSTRACT
Androgen deprivation therapy (ADT) using gonadotropin?releasing hormone agonist (s) (GnRH?A) remains the backbone of advanced prostate cancer treatment. In this review, we assessed the efficacy, safety, and convenience of administration of various GnRH?A. All GnRH?A (goserelin, triptorelin, buserelin, histrelin, and leuprorelin) have comparable potential to suppress testosterone (T) levels (?50 ng/dL in a month and ?20 ng/dL in 3 months). However, goserelin has shown better efficacy in maintaining T levels ?50 ng/dL compared with leuprolide. The incidences of T escape are lower with goserelin and leuprolide than buserelin. Goserelin also has maximum benefit in prostate?specific antigen suppression. In neoadjuvant setting, when only goserelin was used, the 10?year overall survival (OS) rate was 42.6% to 86%. When either goserelin or leuprolide was used, the 10?year OS rate was 62%. As an adjuvant to radical prostatectomy, goserelin had a 10?year survival rate of 87%, and triptorelin had an 8?year survival rate of 84.6%. Goserelin further showed an absolute survival rate of 49% when used as an adjuvant to radiotherapy. The survival rates further improved when GnRH?A are used as combined androgen blockade compared with monotherapy. The frequency and severity of adverse events (hot flushes, fatigue, sexual dysfunction) are comparable among the GnRH?A. Goserelin appears to be the most convenient of all the GnRH?A for administration. Lack of conclusive comparative evidence makes it imperative to have a holistic approach of considering the patient profile and the disease characteristics to select the appropriate GnRH?A for ADT in prostate cancer.