Comparative Study Randomized Controlled Trial

Authors: Olivia Pagani, Meredith M Regan, Barbara A Walley...

BACKGROUND

Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer.

METHODS

In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials.

RESULTS

After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women.

CONCLUSIONS

In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).

Topics: Adult; Androstadienes; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Estradiol; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Mastectomy; Middle Aged; Osteoporosis; Premenopause; Quality of Life; Tamoxifen; Triptorelin Pamoate

PubMed: 24881463
DOI: 10.1056/NEJMoa1404037

Comparative Study

Effectiveness of three different luteinizing hormone-releasing hormone agonists in the chemical castration of patients with prostate cancer: Goserelin versus triptorelin versus leuprolide.

Authors: Myungsun Shim, Woo Jin Bang, Cheol Young Oh...

PURPOSE

To investigate the changes in testosterone levels and rates of chemical castration following androgen-deprivation therapy (ADT) with goserelin, triptorelin, and leuprolide.

MATERIALS AND METHODS

We retrospectively reviewed the medical records of 125 patients with prostate cancer treated with luteinizing hormone-releasing hormone (LHRH) agonists between January 2009 and December 2015. Changes in testosterone concentration during 9 months of ADT with goserelin 11.34 mg, triptorelin 11.25 mg, and leuprolide 11.25 mg were analyzed using a mixed model. The number of patients with serum testosterone below castration levels defined as various values (<50 ng/dL, <20 ng/dL, or <10 ng/dL) at 3, 6, and 9 months were also evaluated.

RESULTS

Of the 125 patients, 59 received goserelin, 44 received triptorelin, and 22 received leuprolide, respectively. The lowest mean testosterone levels during 9 months of treatment were achieved in patients treated with triptorelin, followed by those treated with leuprolide, and then by those treated with goserelin (p=0.001). Significant differences in chemical castration levels were observed only at <10 ng/dL, with 54.2% of goserelin, 93.2% of triptorelin, and 86.4% of leuprolide treated patients (p<0.001).

CONCLUSIONS

Three LHRH agonists showed comparable efficacy for achieving castration when the castration threshold was 50 or 20 ng/dL. However, triptorelin was the most potent LHRH agonist, achieving the lowest mean testosterone levels and the highest rate of chemical castration at <10 ng/dL testosterone.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate

PubMed: 31294133
DOI: 10.4111/icu.2019.60.4.244

Authors: Olivia Pagani, Prudence A Francis, Gini F Fleming...

PURPOSE

The Tamoxifen and Exemestane Trial (TEXT)/Suppression of Ovarian Function Trial (SOFT) showed superior outcomes for premenopausal women with hormone receptor (HR)-positive breast cancer treated with adjuvant exemestane plus ovarian function suppression (OFS) or tamoxifen plus OFS versus tamoxifen alone. We previously reported the magnitude of absolute improvements in freedom from any recurrence across a continuous, composite measure of recurrence risk to tailor decision making. With longer follow-up, we now focus on distant recurrence.

METHODS

The TEXT/SOFT HR-positive/human epidermal growth factor receptor 2 (HER2)-negative analysis population included 4,891 women stratified by predetermined chemotherapy use. Kaplan-Meier estimates of 8-year freedom from distant recurrence were analyzed using subpopulation treatment effect pattern plot (STEPP) methodology across subpopulations defined by the continuous composite measure of recurrence risk. For each patient, the composite risk value was obtained from a Cox model that incorporated age; nodal status; tumor size; grade; and estrogen receptor, progesterone receptor, and Ki-67 labeling index expression levels.

RESULTS

The overall rate of 8-year freedom from distant recurrence was 91.1% and ranged from approximately 100% to 63% across lowest to highest composite risks. TEXT patients who received chemotherapy had an average absolute improvement with exemestane plus OFS versus tamoxifen plus OFS of 5.1%, and STEPP analysis showed improvements from less than 1% to more than 15% from lowest to highest composite risks. SOFT patients who remained premenopausal after chemotherapy had an average 5.2% absolute improvement with exemestane plus OFS versus tamoxifen and reached 10% across composite risks; for tamoxifen plus OFS versus tamoxifen, the maximum improvement was approximately 3.5%. Women who did not receive chemotherapy had a more than 97% rate of 8-year freedom from distant recurrence, and improvements with exemestane plus OFS ranged from 1% to 4%.

CONCLUSION

Premenopausal women with HR-positive/HER2-negative breast cancer and high recurrence risk, as defined by clinicopathologic characteristics, may experience a 10% to 15% absolute improvement in 8-year freedom from distant recurrence with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone. The potential benefit of escalating endocrine therapy versus tamoxifen alone is minimal for those at low recurrence risk.

Topics: Androstadienes; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Female; Humans; Neoplasm Recurrence, Local; Ovariectomy; Ovary; Premenopause; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Triptorelin Pamoate

PubMed: 31618131
DOI: 10.1200/JCO.18.01967

Comparative Study

Authors: Stefania Lasorella, Rossella Porto, Maria Laura Iezzi...

The aim of this study is to compare the clinical and biochemical outcomes of triptorelin acetate (TPA) versus triptorelin pamoate (TPP) treatment in girls with central precocious puberty. A total of 60 patients with idiopathic CPP were retrospectively recruited. Thirty girls were treated with triptorelin acetate 3.75 mg/month (TPA group) and thirty girls in a second group received triptorelin pamoate 3.75 mg/4 weeks (TPP group). Patient follow-up at 12 and 24 months included GnRH Test at 12 months and baseline LH at 24 months. Patients were monitored with pelvic ultrasound, X-Ray of the hand and wrist and anthropometric evaluations. A total of 60/60 girls showed a good response to both formulations. Significant reductions in basal and LH peaks, estradiol values, breast pubertal stage, progression of bone age and growth velocity rate after 12 months treatment were obtained in both groups, demonstrating the equivalence of the two formulations in regulating the hypothalamic-pituitary-gonadal (HPG) axis. Triptorelin pamoate provided a more effective and significant reduction in LH peak after 12 months in comparison with triptorelin acetate more effective in reducing ovarian volume and endometrial thickness. Both formulations were equivalent, even though the LH peak was significantly lower in girls treated with triptorelin pamoate.

Topics: Age Determination by Skeleton; Breast; Child; Female; Humans; Hypothalamic Diseases; Ovary; Puberty, Precocious; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate; Uterus

PubMed: 31441342
DOI: 10.1080/09513590.2019.1655726

Authors: Kuan-Hao Tsui, Li-Te Lin, Peng-Hui Wang...

Topics: Female; Follicle Stimulating Hormone; Humans; Luteal Phase; Male; Oocytes; Pregnancy; Sperm Injections, Intracytoplasmic; Triptorelin Pamoate

PubMed: 25027751
DOI: 10.1016/j.jcma.2014.06.002

Review

Authors: M Lippi, F Orsini, F Damato...

Since 2018, the Italian National Committee for Bioethics (CNB) has endorsed the off-label use of triptorelin, a gonadotropin-releasing hormone agonist (GnRHa), for managing adolescent gender dysphoria (GD). Administered to suppress puberty, triptorelin provides adolescents time to explore their gender identity without the distress of developing secondary sexual characteristics. However, concerns persist regarding its long-term effects on bone density, brain development, and fertility. Ethical debates focus on the validity of informed consent in minors, given their cognitive and emotional immaturity, and the critical role of families in decision-making. The Italian medical-psychiatric model, requiring a formal GD diagnosis and multidisciplinary over-sight, contrasts with the autonomy-centered informed consent model used elsewhere. This paper advocates for a hybrid approach, integrating strengths of both models to ensure safe, accessible, and individualized care. Further research is essential to clarify the efficacy and risks of triptorelin, ensuring evidence-based, fully informed decisions for adolescents with GD.

Topics: Humans; Triptorelin Pamoate; Adolescent; Gender Dysphoria; Italy; Female; Male; Informed Consent; Gonadotropin-Releasing Hormone; Off-Label Use

PubMed: 40109078
DOI: 10.7417/CT.2025.5186

Authors: Xiaoyan Lu, Yiying Sun, Meishan Han...

Triptorelin is a first-line drug for assisted reproductive technology (ART), but the low bioavailability and frequent subcutaneous injection of triptorelin impair the quality of life of women preparing to become pregnant. We report silk fibroin (SF)-based microneedles (MNs) for transdermal delivery of triptorelin-loaded nanoparticles (NPs) to improve bioavailability and achieve safe and efficacious self-administration of triptorelin. Triptorelin was mixed into an aqueous solution of SF with shear force to prepare NPs to control the release and avoid the degradation of triptorelin by enzymes in the skin. Two-step pouring and centrifugation were employed to prepare nanoparticles-encapsulated polymeric microneedles (NPs-MNs). An increased β-sheet content in the conformation ensured that NPs-MNs had good mechanical properties to pierce the stratum corneum. Transdermal release of triptorelin from NPs-MNs was increased to ∼65%. The NPs-MNs exhibited a prolonged drug half-life and increased relative bioavailability after administration to rats. Surging levels of luteinizing hormone and estradiol in plasma and their subsequent prolonged downregulation indicate the potential therapeutic role of NPs-MNs in ART regimens. The triptorelin-loaded NPs-MNs developed in this study may reduce the physical and psychological burden of pregnant women using ART regimens.

Topics: Female; Humans; Pregnancy; Animals; Rats; Quality of Life; Triptorelin Pamoate; Skin; Biological Availability; Fibroins; Nanoparticles

PubMed: 37387211
DOI: 10.1080/10717544.2023.2226367

Review

Authors: Junjun Miao, Qianhua Yan, Lijuan Wang...

The impacts of gonadtropin-releasing hormone (GnRH) agonists on thyroid function have long been observed and the conclusions were controversial. We here reported three cases of transient hyperthyroidisms after triptorelin therapy. The three patients showed decreased thyroid-stimulating hormone (TSH), with or without elevated free triiodothyronine (FT3) and free thyroxine (FT4) 2 weeks after injection of triptorelin. Thyroid-specific autoantibody assays showed antithyroid microsome autoantibody (TMAb) and (or) antithyroglobulin autoantibody (TgAb) were positive in two patients while and antithyrotropin receptor autoantibody (TRAb) were negative in all three cases. One patient with all thyroid-specific autoantibodies negative showed enlarged thyroid in thyroid ultrasound scanning. Only mild symptoms of hyperthyroidism presented in one patient. Four weeks after triptorelin injection, thyroid function returned to normal in all three patients. These observations indicated transient hyperthyroidism due to thyroid destruction in patients receive triptorelin therapy. The hyperthyroidism was most possibly due to onset of the autoimmune thyroiditis, emphasizing monitoring thyroid function during triptorelin treatment in females.

Topics: Adult; Autoantibodies; Female; Humans; Hyperthyroidism; Thyroid Function Tests; Thyrotropin; Thyroxine; Triiodothyronine; Triptorelin Pamoate

PubMed: 29484896
DOI: 10.1080/09513590.2018.1445710

Randomized Controlled Trial

Authors: Xiaoyan Li, Huaifang Li, Hong Shi...

INTRODUCTION

This phase 3, randomized, open-label, active-controlled, multicenter study investigated the efficacy of triptorelin pamoate prolonged-release (PR) 3-month in Chinese patients with endometriosis by demonstrating the noninferiority of the 3-month formulation to the standard of care, triptorelin acetate PR 1-month.

METHODS

The trial was conducted in 24 clinical centers in China, and included 300 Chinese women (18-45 years) with endometriosis and regular menstrual cycles who required treatment with a gonadotropin-releasing hormone agonist for 6 months. One group of patients (n = 150) was treated with triptorelin pamoate PR 3-month (15 mg per injection, once every 12 weeks), and the other (n = 150) with triptorelin acetate PR 1-month (3.75 mg per injection, once every 4 weeks). The primary outcome measure was the proportion of patients with estradiol (E2) concentrations suppressed to castration levels (≤ 184 pmol/L, or 50 pg/mL) after 12 weeks of treatment.

RESULTS

Triptorelin pamoate PR 3-month was noninferior to triptorelin acetate PR 1-month for the treatment of endometriosis: over 98% of patients in both groups were chemically castrated at week 12. Both formulations were also equally efficacious in reducing endometriosis-associated pelvic pain, and reducing serum concentrations of E2, luteinizing hormone, and follicle-stimulating hormone over time. No new safety concerns were identified.

CONCLUSION

Triptorelin pamoate PR 3-month is a valid alternative to triptorelin acetate PR 1-month for the treatment of Chinese women with endometriosis, with fewer injections and a potentially lower burden of care.

TRIAL REGISTRATION

NCT03232281.

Topics: Acetates; Endometriosis; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Triptorelin Pamoate

PubMed: 35947347
DOI: 10.1007/s12325-022-02264-5

Review

Authors: Huan Song, DongHao Lu, Kate Navaratnam...

BACKGROUND

Uterine fibroids, also called uterine leiomyomas or myomas, are the most common benign tumours in women of reproductive age. Albeit generally benign, uterine fi broids can have a major impact on women's health and quality of life by contributing to abnormal uterine bleeding and causing pelvic pressure symptoms (such as increased urinary frequency, pelvic pain and constipation). Traditional treatments for symptomatic fi broids include a variety of surgical techniques. However, because of the high recurrence rate, as well as possible pain and infertility caused by the formation of postoperative adhesions, this approach may not be advisable. Safer and more effective medical therapy has long been awaited. Both in vitro studies and clinical trials have suggested that use of the aromatase inhibitors (AIs), a class of anti-oestrogens, might inhibit fi broid growth, thereby eliminating the need for surgery.

OBJECTIVES

To evaluate the effectiveness and safety of aromatase Inhibitors (AIs) in women with uterine fibroids.

SEARCH METHODS

We searched the following databases (from inception to August 21, 2013): Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL and PsycINFO. In addition, the reference lists of included trials were searched, and experts in the field were contacted.

SELECTION CRITERIA

Randomised controlled trials (RCTs) in women of reproductive age comparing the effects of any AI versus placebo, no treatment or any medical treatment/surgery were included.

DATA COLLECTION AND ANALYSIS

Selection of eligible trials, assessment of trial quality and data extraction were performed independently by two review authors. If data were available, we planned to calculate odds ratios (ORs) for analysis of dichotomous data and mean differences for continuous data, with 95% confidence intervals (CIs).

MAIN RESULTS

Only one trial involving 70 participants was included. This trial did not report our primary review outcome (relief of symptoms of fibroids). The only secondary review outcomes reported by this trial were adverse effects (hot flushes) and reduction in fibroid size. Significantly fewer women reported hot flushes in the letrozole group than in the GnRHa group (0/33 vs 26/27, P < 0.05). Use of letrozole reduced fibroid volume by 46% and use of a gonadotrophin-releasing hormone (GnRH) agonist (GnRHa) by 32% after 12 weeks of treatment; these proportions were not significantly different. The included trial did not report data on fibroid volume in a form that permitted calcuation of an odds ratio. Morevoer it was unblinded and included only 60/70 women in analysis.

AUTHORS' CONCLUSIONS

Evidence is insufficient to support the use of AI drugs in the treatment of women with uterine fibroids.

Topics: Antineoplastic Agents; Aromatase Inhibitors; Female; Hot Flashes; Humans; Leiomyoma; Letrozole; Nitriles; Triazoles; Triptorelin Pamoate; Uterine Neoplasms

PubMed: 24151065
DOI: 10.1002/14651858.CD009505.pub2