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Triptorelin in the Treatment of Prostate Cancer

Clinical Efficacy and Tolerability

  • Review Article
  • Published:
American Journal of Cancer

Abstract

Triptorelin is a synthetic analog of gonadotropin-releasing hormone (GnRH; also known as luteinizing hormone-releasing hormone [LHRH]), which has enhanced receptor affinity, extended half-life and increased bioactivity. Triptorelin initially stimulates the pituitary gland, increasing serum luteinizing hormone and testosterone levels; however, after 3–4 weeks, the pituitary becomes refractory due to receptor desensitization and/or down-regulation, resulting in castration levels of testosterone in men and postmenopausal estradiol levels in women.

Pharmacologic equivalence studies have shown that triptorelin, buserelin and goserelin are equally effective in down-regulating the pituitary-gonadal axis, and the new 3- and 1-month depot formulations of triptorelin have equal efficacy. In men with locally advanced or metastatic prostate cancer, administration of triptorelin leads to subjective improvement in lower urinary tract symptoms and pain, as well as objective responses such as decreased serum levels of acid and alkaline phosphatase and prostate-specific antigen, decreased prostate volume, and regression of skeletal metastases.

Randomized clinical trials comparing triptorelin with bilateral orchidectomy have shown no significant differences in clinical response, survival or side effects. The time to subjective response was shorter in patients treated with orchidectomy, but there was a trend towards reduced psychologic morbidity in those treated with triptorelin. In randomized clinical trials comparing triptorelin with leuprolide (leuprorelin), two studies concluded that triptorelin induced a more rapid decrease in testosterone levels, although both drugs had similar clinical efficacy, whereas a third study concluded that triptorelin reduced testosterone levels less rapidly than, but maintained castration levels of testosterone as effectively as, leuprolide. The 9-month survival rate was significantly higher for triptorelin (97% vs 90.5% for leuprorelin).

Neoadjuvant triptorelin treatment in localized prostate cancer prior to radical prostatectomy may reduce the incidence of positive surgical margins, but no survival advantage has been demonstrated. Neoadjuvant treatment before radiotherapy, by reducing prostatic volume, may decrease radiation-related complications, and may increase survival in a subset of patients with a Gleason score of 2–6.

The most common adverse effects of triptorelin and GnRH agonists in general, are hot flushes, loss of libido, and impotence. The initial increase in serum testosterone levels — the ‘flare’ phenomenon — may lead to exacerbation of bone pain, paraplegia and (rarely) death in patients with a large tumor burden. Androgen deprivation leads to a reduction in bone mineral density of 3–5% per year, but it remains to be proven that this significantly increases the clinical fracture risk in patients with prostate cancer.

In conclusion, the clinical efficacy and tolerability of triptorelin in the treatment of prostate cancer are similar to that of surgical castration and leuprolide.

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    Chris F. Heyns

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Heyns, C.F. Triptorelin in the Treatment of Prostate Cancer. Am J Cancer 4, 169–183 (2005). https://doi.org/10.2165/00024669-200504030-00004

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