Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer

OBJECTIVE: To compare the efficacy of monthly administrations of the luteinizing hormone-releasing hormone agonists triptorelin pamoate and leuprolide acetate to induce and maintain castrate levels of serum testosterone in men with advanced prostate cancer. PATIENTS AND METHODS: Men with advanced prostate cancer were randomly assigned to receive triptorelin 3.75 mg or leuprolide 7.5 mg. The agent was injected intramuscularly every 28 days for nine injections. Primary endpoints were the percentages of men whose serum testosterone concentrations declined to and were maintained at or below castrate levels (≤ 1.735 nmol/L or ≤500 ng/L) during 9 months (253 days) of treatment. Secondary endpoints were luteinizing hormone levels, bone pain, prostate specific antigen levels, quality of life, testosterone pharmacodynamics, survival, and safety variables. RESULTS: In all, 284 men received either triptorelin (140) or leuprolide (144). The percentage of men with castrate levels of serum testosterone was lower at 29 days for triptorelin than for leuprolide (91.2% vs 99.3%; point estimate -8.0, 95% confidence interval -16.9% to -1.4%), but equivalent at 57 days (97.7% vs 97.1%). The mean (98.8% vs 97.3%) and cumulative (96.2% vs 91.2%) castration maintenance rates between 29 and 253 days were equivalent between the treatment groups. Secondary endpoints were equivalent between treatment groups except for the 9-month survival rate, which was significantly higher for triptorelin than for leuprolide (97.0% vs 90.5%; P = 0.033). Both treatments were well tolerated. CONCLUSION: Triptorelin reduced testosterone concentrations less rapidly, but maintained castration as effectively as leuprolide. There was no evidence that the slower onset of castration caused deleterious effects.Articl

Triptorelin 6-month formulation in the management of patients with locally advanced and metastatic prostate cancer: An open-label, non-comparative, multicentre, phase III study

Background and Objectives: Triptorelin 6-month formulation was developed to offer greater convenience to both patients and physicians by reducing the injection frequency. The efficacy, pharmacokinetics and safety of a new 6-month formulation of triptorelin were investigated over 12 months (48 weeks). The primary objective was to evaluate the formulation in achieving castrate serum testosterone levels (≤1.735 nmol/L or ≤50 ng/dL) on day 29 and in maintaining castration at months 2-12. Absence of luteinizing hormone (LH) stimulation and change in prostate-specific antigen (PSA) level were also assessed. Methods: An open-label, non-comparative, phase III study in 120 patients with advanced prostate cancer was conducted from July 2006 to August 2007 in private and public institutions in South Africa. Each patient received two consecutive intramuscular injections of triptorelin embonate (pamoate) 22.5mg at an interval of 24 weeks. In all patients, testosterone (primary outcome measurement) was measured at baseline and then every 4 weeks; LH was measured before and 2 hours after the two injections. PSA was measured on day 1 and at weeks 12, 24, 36 and 48. Adverse events were recorded at each visit. Results: In the intent-to-treat population, 97.5% (95% CI 92.9, 99.5) of patients achieved castrate serum testosterone levels by day 29, and 93.0% (95% CI 86.8, 97.0) maintained castration at months 2-12. After the second injection, 98.3% of patients showed absence of LH stimulation. The most frequent drug-related adverse events were hot flushes (71.7% of patients). No patient withdrew from the study as a result of an adverse event. Conclusions: The triptorelin 6-month formulation was well tolerated and was able to achieve and maintain castration for the treatment of locally advanced and metastatic prostate cancer. By reducing the frequency of required injections, this new formulation offers a more convenient treatment regimen. © 2009 Adis Data Information BV. All rights reserved.Articl

Dynamic measurements of serum inhibin B and estradiol: a predictive evaluation of ovarian response to gonadotrophin stimulation in the early stage of IVF treatment

Objective: We dynamically measured serum inhibin B and estradiol in the early stage of hormonal stimulation to predict the ovarian response in in vitro fertilization (IVF) treatment. Methods: A total of 57 patients (<40 years of age) who underwent the first cycle of long protocol IVF or introcytoplasmic sperm injection (ICSI) treatment were included. Serum inhibin B, estradiol, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured four times: (1) on Day 3 of the menstrual cycle (basal); (2) on the day before the first administration of gonadotrophin (Gn) (Day 0); (3) on Day 1 of Gn therapy; and (4) on Day 5 of Gn therapy. Comparisons of these measurements with ovarian responses and pregnancy outcomes were made and analyzed statistically. Results: (1) On Day 1 and Day 5 of recombinant FSH (rFSH) stimulation, ovarian response, i.e., numbers of follicles, oocytes, fertilized oocytes, and embryos, had a positive correlation (r s=0.46~0.61, P=0.000) with raised inhibin B and estradiol concentrations, but a negative correlation (r s=−0.67~−0.38, P=0.000 or P<0.01) with total rFSH dose and total days of rFSH stimulation. (2) No significant variation (P>0.05) between the pregnant and non-pregnant groups on the basis of mean age or on all hormone concentrations at four times of the IVF cycle was observed. However, all the seven patients aged >35 years did not reach pregnancy. Conclusions: (1) Serum inhibin B and estradiol concentrations obtained shortly after Gn therapy may offer an accurate and early prediction of ovarian response; (2) Low levels of serum inhibin B and estradiol obtained shortly after Gn stimulation indicate the need for a longer period of Gn treatment and a higher daily dosage; (3) No obvious pregnancy difference among patients of age <35 years was found; however, IVF pregnancy outcome is significantly lower in women of age >35 years