Goserelin Group Research Articles

Comparison of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer.

Although different gonadotropin-releasing hormone (GnRH) agonists may have different effects, their effect of ovarian protection during chemotherapy for breast cancer has not been compared. This study aimed to compare the effects of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer. This prospective study analyzed 193 patients with breast cancer aged ≤ 40years who had regular menstruation and serum anti-Müllerian hormone (AMH) levels ≥ 1ng/mL before treatment. Patients received either goserelin or leuprorelin for ovarian protection during doxorubicin/cyclophosphamide-based chemotherapy. Resumption of menstruation and changes in serum levels of AMH were compared between the two groups at 12months after completion of chemotherapy. The mean age and the pretreatment serum AMH level were 33.2years and 4.4ng/mL in goserelin group and 34.2years and 4.0ng/mL in leuprorelin group. The proportion of patients who resumed menstruation was not different between the goserelin (94.4%) and leuprorelin (95.3%) groups at 12months after chemotherapy completion. Serum AMH levels decreased significantly in both the goserelin (from 4.4 to 1.2ng/mL) and leuprorelin (from 4.0 to 1.2ng/mL) groups, with no statistical significance. In addition, no difference was found in the proportion of patients with serum AMH levels ≥ 1ng/mL between the goserelin (49.5%) and leuprorelin (44.2%) groups at 12months after chemotherapy. Goserelin and leuprorelin were comparable in terms of ovarian protection during doxorubicin/cyclophosphamide-based chemotherapy in young patients with breast cancer.

Protective effect of goserelin on ovarian reserve during (neo)adjuvant chemotherapy in young breast cancer patients: a prospective cohort study in China.

Does goserelin, a GnRH agonist, have a protective effect in young breast cancer patients in terms of ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) during chemotherapy? Compared with chemotherapy alone, concurrent goserelin is associated with a higher probability of ovarian reserve recovery at 1 year after chemotherapy. Previous studies on the administration of goserelin to protect ovarian function during chemotherapy have produced conflicting results because of the endpoint used, namely, chemotherapy-induced amenorrhoea. Reproductive medicine specialists consider AMH and AFC as the most sensitive ovarian reserve markers; however, they have never been used as biomarkers to assess the potential protective effects on ovarian reserve of goserelin during chemotherapy. This was a prospective cohort study in which patients were assigned to receive (neo)adjuvant chemotherapy with goserelin (the goserelin group) or without goserelin (the control group) according to each patient's preference. Of 242 breast cancer patients enrolled between December 2015 and November 2019, 76 in control group and 73 in goserelin group were able to be assessed at 1 year after chemotherapy. Premenopausal patients with a regular menstrual cycle and aged 18-45 years were eligible for enrolment if they were newly diagnosed with stages I-III breast cancer for which treatment with adjuvant or neoadjuvant chemotherapy was planned. Each patient in the goserelin group was given a subcutaneous dose of 3.6 mg at least 1 week before the first cycle of chemotherapy and then every 4 weeks for the duration of chemotherapy. Ovarian reserve markers and menstrual status were evaluated before and after chemotherapy in the two treatment groups. The primary endpoint was the AMH recovery rate, the secondary endpoints were the recovery rates of AFC, estradiol (E2), follicle-stimulating hormone (FSH) and menstruation. Among 149 patients (76 in the control group and 73 in the goserelin group) with complete data at 1 year after chemotherapy, the adjusted recovery rate of AMH was 46.5% and 21.8% in the goserelin group and control group, respectively (odds ratio: 3.08; P = 0.002). The trends in AFC and FSH recovery rates were consistent with that in AMH recovery rate. Notably, AMH levels remained low in 41.3% of patients whose menstrual activity had resumed. Randomisation was not performed because of ethical considerations, so selection bias was inevitable, although propensity score weighting was done. The study was also underpowered because 21.5% (52/242) of enrolled patients received GnRH agonist-containing endocrine therapy and could not be analysed at 1 and 2 years after chemotherapy. Our results indicate that co-administration of goserelin with chemotherapy provides obvious ovarian reserve protection in these young breast cancer patients. We expect that these results will be applicable in clinical practice for young breast cancer patients. This study was funded by the National Key R&D Program of China No. 2016YFC0901302, by the Research and Development Fund of Peking University People's Hospital No. RD2014-13, RDY2017-19 and by AstraZeneca. The authors have no disclosures. NCT02430103.

258P Goserelin for ovarian protection in premenopausal breast cancer patients receiving cyclophosphamide containing chemotherapy

Globally, breast cancer is the most common female reproductive cancer. Although alkylating chemotherapy is a part of initial treatment in women with curable breast cancer. Premature ovrian insufficiency (POI) is a potential consequence of this treatment and can cause infertility. The current work assessed role of Goserelin in reducing risk of POI in such women. A prospective study was conducted in period between 2017 and 2019 and enrolled 150 women with histologically confirmed breast cancer. Those women were randomly subdivided into two equal groups; Goserelin group where women received chemotherapy regimens with Goserelin and control group where women received chemotherapy regimens without Goserelin. Both groups were followed for one year after end of chemotherapy to assess frequency of POI. Both groups had insignificant differences as regarding baseline data with exception of singnicantly higher negative hormonal receptor among study group. Hot flashes and headache were the most frequent adverse effects in both groups. 12 patients (16%) of Goserelin group and 22 (29%) of the control group developed POI with significant difference (P< 0.05). Median time to resumption of menses was significantly lower among study group in comparison to that control group (5.70 vs. 10.60 months; P= 0.03). Based on the current, older age increased risk to POI while negative hormonal receptors and addition of Goserelin were reducing the frequency of POI. Goserelin co-treatment with regimens of chemotherapy in premenopausal women with breast cancer could reduce the frequency of POI and preserve the fertility among those women.

Abstract P2-12-11: Does goserelin have an effect on quality of life in women who have chemotherapy for early breast cancer? Results from the OPTION randomised trial

Abstract The OPTION trial examined whether or not premenopausal women with early breast cancer receiving chemotherapy benefited from ovarian function protection with goserelin. This trial showed some preservation of ovarian function and fertility in women aged 40 years or less*. Additionally the OPTION trial examined the immediate and late impact of treatments on patients’ Quality of Life (QoL) over a 5 year period. Patients and Methods: In the OPTION trial 227 pre-menopausal patients with early stage breast cancer were randomly assigned to chemotherapy with or without goserelin. Patients were stratified by age into ≤40 years and &amp;gt; 40 years of age. QoL was assessed with the Functional Assessment of Cancer Therapy - Breast (FACT-B) and Endocrine Symptom checklist(ES) at baseline (pre- treatment), 3, 6, 12, 18 and 24 months, then annually to 5 years. Results:-Two hundred and thirteen patients were available for analysis of QoL results. There was a temporary increase in endocrine symptoms of menopause in the goserelin group that was statistically higher than in the controls (P = 0.02) and was associated with a decrease in the main outcome measure of global QoL, TOI. This contrasted with a longer term outcome favouring the intervention in terms of QoL and fewer adverse endocrine symptoms, though these later findings were not statistically significant. Conclusions: Cytotoxic chemotherapy with or without goserelin causes a short term decrement in QoL for up to 6 months in otherwise well women.* Ann Onc 2017 28 1811-1816. Citation Format: Robert CF Leonard, Janine Mansi, Ann Yellowlees, Lesley Fallowfield, Valerie Jenkins. Does goserelin have an effect on quality of life in women who have chemotherapy for early breast cancer? Results from the OPTION randomised trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-11.

Efficacy and safety of degarelix in patients with prostate cancer: Results from a phase III study in China

ObjectiveTo establish non-inferiority of gonadotropin-releasing hormone degarelix compared with goserelin in suppressing and maintaining castrate testosterone levels from Day 28 to Day 364 in Chinese patients with prostate cancer. MethodsThis is an open-label, multi-centre study in which men aged ≥18 years were randomised in a 1:1 ratio to once-a-month subcutaneous injection of either degarelix (240/80 mg) or goserelin (3.6 mg) for 12 months. The primary endpoint was difference in 1-year cumulative probability of suppressing testosterone to ≤0.5 ng/mL. Non-inferiority was to be established if the lower 95% confidence interval (CI) limit for difference in cumulative probability between the treatment arms was greater than −10%. Secondary endpoints included cumulative probability of prostate-specific-antigen-progression-free-survival (PSA-PFS). Safety was also assessed. ResultsBaseline demographics and disease characteristics were similar between degarelix (n=142) and goserelin (n=141) treatment arms. The difference in cumulative probability of maintaining castrate levels from Day 28–364 was 3.6% (95% CI:−1.5%, 8.7%), demonstrating non-inferiority of degarelix. The cumulative probability of PSA-PFS at Day 364 was higher for degarelix (82.3%, 95% CI: 74.7%, 87.7%) versus goserelin (71.7%, 95% CI: 63.2%, 78.5%, p=0.038). Adverse events (AEs) were similar between treatment arms, except for more injection site reactions with degarelix versus goserelin. Four (2.8%) and nine (6.4%) patients discontinued due to AEs in degarelix and goserelin groups, respectively. ConclusionDegarelix was non-inferior to goserelin in achieving and maintaining testosterone suppression at castrate levels during 1-year treatment. PSA-PFS was significantly higher with degarelix, suggesting improved disease control. Both treatments were well tolerated.

Long-term Surgical and Chemical Castration Deteriorates Memory Function Through Downregulation of PKA/CREB/BDNF and c-Raf/MEK/ERK Pathways in Hippocampus.

PurposeGoserelin is a drug used for chemical castration. In a rat model, we investigated whether surgical and chemical castration affected memory ability through the protein kinase A (PKA)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) and c-Raf/mitogen-activated protein kinases-extracellular signal–regulated kinases (MEK)/extracellular signal–regulated kinases (ERK) pathways in the hippocampus.MethodsOrchiectomy was performed for surgical castration and goserelin acetate was subcutaneously transplanted into the anterior abdominal wall for chemical castration. Immunohistochemistry was done to quantify neurogenesis. To assess the involvement of the PKA/CREB/BDNF and c-Raf/MEK/ERK pathways in the memory process, western blots were used.ResultsThe orchiectomy group and the goserelin group showed less neurogenesis and impaired short-term and spatial memory. Phosphorylation of PKA/CREB/BDNF and phosphorylation of c-Raf/MEK/ERK decreased in the orchiectomy and goserelin groups.ConclusionsShort-term memory and spatial memory were affected by surgical and chemical castration via the PKA/CREB/BDNF and c-Raf/MEK/ERK signaling pathways.

Anti-Müllerian hormone as a new marker of the ovarian reserve function preservation by goserelin during (neo)adjuvant chemotherapy for young breast cancer patients

To observe the dynamic change of anti-Müllerian hormone (AMH) in 1 year after chemotherapy which is the best biochemical marker of ovarian reserve in reproductive medicine setting and to evaluate the effect of gonadotropin-releasing hormone agonist (GnRHa)goserelin to prevent ovarian reserve function during (neo)adjuvant chemotherapy for young breast cancer patients. Between December 2015 and June 2017, 101 breast cancer patients of age ≤ 45 years with stages I to III had been enrolled. The patients were assigned without interference to receive either (neo) adjuvant chemotherapy with goserelin (goserelin group) or without goserelin (chemotherapy group) as their own selection. AMH and menstrual status were evaluated before, during and 0.5 year, 1 year after chemotherapy. Primary end point was the incidence of low AMH value (<0.4 μg/L) at the end of 1 year. Secondary end point was the incidence of amenorrhea (the absence of menses in the preceding 12 months after assignment). In the study, 51 patients chose to join the chemotherapy group, while the other 50 patients selected goserelin to preserve their ovarian reserve function. More unmarried or childless, hormone receptors negative,receiving breast conservation therapy patients with earlier stage selected goserelin before chemotherapy. The incidence of low AMH value was significantly higher in chemotherapy group than in goserelin group (74.5% vs. 38.0%, P<0.001) in 1 year after chemotherapy. The incidence of amenorrhea was consistent with AMH (56.9% vs. 24.0%, P=0.001). And more patients' menstruation (78.9% vs. 54.5%) and AMH value (71.0% vs. 53.8%) recovered in goserelin group within 6 months after chemotherapy. In subgroup analysis, AMH and menstruation seemingly recovered more in goserelin group independent of age, chemotherapy regimen and use of tamoxifen. Especially, AMH value of 36.4% (8/22) patients in chemotherapy group and 18.4% (7/38) patients in goserelin group still maintained low level (<0.4 μg /L) although their menstruation had recovered 1 year after chemotherapy. In addition, 41 patients (20 patients in chemotherapy group, 21 patients in goserelin group) could be evaluated for the dynamic change of AMH and menstrual status during chemotherapy. The mean level of AMH in chemotherapy group declined rapidly to very low level before the 3rd cycle, while 70% of the patients kept presence of menstruation. At the same time, the mean level of AMH in goserelin group was still above 0.4 μg /L, but all of the patients had menopause. Our study has offered evidence that Goserelin with chemotherapy could protect against ovarian reserve failure for young breast cancer patients, now that more patients' AMH value recovered earlier who had selected co-treatment. AMH may be a more precise marker than menstrual status to clinically evaluate ovarian reserve function pre-, during and post- chemotherapy.

Oral contraceptives for pain associated with endometriosis.

Oral contraceptives for pain associated with endometriosis.

Abstract P1-15-01: Final analysis of SWOG S0230/Prevention of early menopause study (POEMS)

Abstract BACKGROUND: The SWOG S0230/POEMS study demonstrated a 70% reduction in ovarian failure (OF) with goserelin coadministration during chemotherapy (CT) for ER-negative early breast cancer (BC; Moore H et al, NEJM 2015). Goserelin use was also associated with more pregnancies as well as favorable disease free survival (DFS) and overall survival (OS). Here we report the final analysis after 5 years of follow-up. METHODS: Premenopausal women age &amp;lt;50 with stage I-IIIA ER/PR-negative BC to be treated with cyclophosphamide-containing CT were randomized to receive standard CT with or without monthly goserelin 3.6 mg SQ starting at least 1 week prior to the first CT dose. The primary endpoint was OF at 2-years, defined as amenorrhea for the prior 6 months and post-menopausal FSH. Secondary endpoints included pregnancies, disease free survival (DFS) and overall survival (OS). An unplanned analysis of rate of menses recovery at 2 years (presence of menses within 6 months of the 2 year time-point or pregnancy within the first 2 years) was also conducted. OF and pregnancy endpoints were analyzed using multivariable logistic regression adjusting for stratification factors (age and CT regimen); DFS and OS were examined using multivariable Cox regression, adjusting for stratification factors and stage. Two-sided p-values are reported unless otherwise specified in accordance with protocol design. RESULTS: Among 257 randomized participants, 218 were eligible and evaluable. One hundred thirty-six eligible and evaluable patients had OF data and 186 had menstrual data. Median age was 37.7 years. Among the 136 patients with OF data, the odds ratio (OR) for OF at 2 years was 0.30 (95% CI 0.1-0.98; one-sided p=0.023) comparing CT with goserelin to standard CT alone. Among 186 patients with menstrual data, 80% recovered menses by 2 years in the goserelin arm compared with 70% in the standard arm (OR=1.74, 95% CI: 0.83-3.66, p=0.15). Pregnancies, DFS and OS are reported for all 218 eligible and evaluable patients. With a median follow-up of 5.1 years, 22% of patients in the goserelin group had at least one pregnancy compared with 12% in the standard group (OR 2.38, 95% CI 1.08-5.26, p=0.03). Cumulative incidence of pregnancy at 5 years is 23% in the goserelin arm compared with 12% in the standard group. Five-year Kaplan-Meier DFS estimates are 88% in the goserelin arm compared with 79% in the standard arm (HR=0.50, p=0.05). Five-year OS is 92% with goserelin versus 83% in the standard arm (HR=0.47, p=0.06). Including all 257 randomized patients, HR for DFS and OS are 0.67 and 0.48 (p=0.18 and p=0.05). CONCLUSION: Ovarian suppression with goserelin during chemotherapy for hormone receptor-negative breast cancer reduces OF risk and, after 5 years of follow-up, continues to be associated with more pregnancies and improved survival compared with chemotherapy without goserelin. SUPPORT: NIH/NCI grant awards CA189974, CA180888, CA180819, CA074362; AstraZeneca Citation Format: Moore HCF, Unger JM, Phillips K-A, Boyle F, Hitre E, Moseley A, Porter D, Francis PA, Goldstein LJ, Gomez HL, Vallejos CS, Partridge AH, Dakhil SR, Garcia AA, Gralow J, Lombard JM, Forbes JF, Martino S, Barlow WE, Fabian CJ, Minasian L, Meyskens FL, Gelber RD, Hortobagyi GN, Albain KS. Final analysis of SWOG S0230/Prevention of early menopause study (POEMS) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-15-01.

GnRH agonist for protection against ovarian toxicity during chemotherapy for early breast cancer: the Anglo Celtic Group OPTION trial

Chemotherapy-induced premature ovarian insufficiency (POI) impacts fertility and other aspects of women's health. The OPTION trial tested whether administration of a gonadotropin-releasing hormone agonist during chemotherapy for early breast cancer reduced the risk of POI. This was a prospective, randomized, parallel group study of the gonadotropin-releasing hormone agonist goserelin administered before and during chemotherapy for breast cancer with stage I-IIIB disease. The primary outcome was amenorrhoea between 12 and 24 months after randomization, supported by elevated follicle stimulating hormone concentrations to give an additional analysis as rate of POI. A total of 227 patients were randomized and the primary analysis was conducted on 202 patients. Goserelin reduced the prevalence of amenorrhoea between 12 and 24 months to 22% versus 38% in the control group (P = 0.015) and the prevalence of POI to 18.5% versus 34.8% in the control group (P = 0.048). Follicle stimulating hormone concentrations were also lower in all women treated with goserelin at both 12 and 24 months (P = 0.027, P = 0.001, respectively). The effect of goserelin was not statistically significant in women >40 years. Assessment of the ovarian reserve using anti-Müllerian hormone showed a marked fall in both groups during treatment to median values of 5% of pretreatment levels in the control group and 7% in the goserelin group, which were not significantly different between groups. This study shows that goserelin reduced the risk of POI in women treated with chemotherapy for early breast cancer, with particular efficacy in women aged ≤40 years old. The degree of ovarian protection also seems limited and the clinical significance for fertility and longer term prevention of estrogen deficiency-related outcomes needs to be determined.

Goserelin versus Norethisterone in the Management of Menorrhagia with Uterine Fibroid

Menorrhagia is common in patients with uterine fibroids, if operation needs to be delayed for a particular reason, goserelin can be used safely to reduce bleeding and the size of the tumor.The objective is to compare between goserelin acetate and norethisterone on patients with menorrhagia and uterine fibroid. A randomized controlled study conducted in Elwiya maternity teaching hospital, Baghdad from the first of November 2007 to the end of April 2009. 90 patients from the consultant outpatient clinic with menorrhagia and fibroid, and their operations were delayed for medical reason were allocated in two groups, the first group, was given 3.2 mg goserelin acetate subcutaneously monthly for 3 months and the second group was given 5 mg norethisterone orally three times daily during the attack of bleeding and 5 mg once daily, cyclically if no bleeding for 3 months. The fibroid was measured in two dimensions, using convex real-time ultrasound before treatment and three months after treatment. Haemoglobin and the number of pads used were also reported before and after treatment, also the side effects in both groups and the need for operations.The size of fibroid in two dimensions measurement was reduced from 28.24 cm2 ± 6.14 to 12.3 cm2 ± 3.45 in the goserelin group (P=0.0001) versus 26.56 cm2 ± 5.96 to 25.22 cm2 ± 5.01 in the norethisterone group (P= 0.2589). The haemoglobin level was 9.28 gm/100ml ± 2.44 pre-treatment in the goserelin group and 11.2 gm/100ml ± 1.88 post-treatment (P= 0.0001) versus 10.08 gm/100ml ± 2.86, and 10.24 gm/100ml ± 2.46 respectively in the norethisterone group (P= 0.7798). The need for operation was decreased significantly in the goserelin group. Goserelin showed better patient response and reduction in the tumor size than norethisterone in treatment of patients with menorrhagia and uterine fibroids if operation is delayed for medical or other reasons.&#x0D; Key words: Goserelin, Norethisterone , Menorrhagia, Uterine Fibroid

Abstract P5-11-05: Examining bone degeneration as a side effect of treatment in premenopausal breast cancer patients

Abstract Background: Although it is widely known that adjuvant treatments cause osteoporosis in postmenopausal women, the effect of treatment and the exact degree of bone loss in premenopausal women is not well understood. For this reason, this study examined the relationship between the changes of bone mineral density(BMD) and the types of treatment in premenopausal breast cancer patients. Method: This retrospective study looks at preoperative and annual spine bone densitometry tests conducted on breast cancer patients during their observational period following initial treatment for their diagnosis. 461 premenopausal patients who received treatment from January 2006 to April 2007 were the study cohort because of the availability of bone mineral density (BMD) data (L-spine and femur T scores) for a two-year period. The data from the patients were separated into groups according to their treatment plans: observation, adjuvant chemotherapy, adjuvant chemotherapy followed by use of Tamoxifen, and GnRHa(Gonadotropin Releasing Hormone agonist) followed by Tamoxifen. Results: Of the 461 patients, 21 received no treatment aside from surgery, 75 received only Tamoxifen, 34 only chemotherapy, 166 chemotherapy and Tamoxifen, and 165 Zoladex and Tamoxifen. The no treatment group demonstrates the standard annual change in BMD. At first year, the chemotherapy only group and tamoxifen after chemotherapy group showed significant bone loss in the first year (p&amp;lt;0.005, both). The patients who received tamoxifen alone or tamoxifen with goserelin showed decrease BMD but not significant. After 2 years, tamoxifen with goserelin group showed significant decreased BMD in both spine and femur (p&amp;lt;0.001, p=0.001, both). Chemotherapy group showed partial recovery from the first year bone loss. Conclusion: The patients who received chemotherapy or GnRHa as treatment showed the greatest degree of bone degeneration but at different periods. However, Tamoxifen used along with these treatments seemed to lessen the extent of bone degeneration. Significant bone loss from hormone treatment occurred two years after surgery as compared to one year for chemotherapy. Citation Format: Kim M, Kim HJ. Examining bone degeneration as a side effect of treatment in premenopausal breast cancer patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-05.

Dienogest compared with gonadotropin-releasing hormone agonist after conservative surgery for endometriosis.

Although there are various hormone therapies, including gonadotropin-releasing hormone agonist, danazol, levonorgestrel-releasing intrauterine system, dienogest, and low-dose estrogen progestin, no consensus opinion has been reached in terms of which medication should be used and for how long it should be administered. We aimed to determine whether dienogest or goserelin is the better postoperative therapy to prevent recurrence of endometriosis. A prospective cohort randomized study were conducted, including 198 patients diagnosed as having endometriosis. A total of 111 patients were randomly assigned into two groups: the dienogest-administered group (n=56) and the goserelin-administered group (n=55). Patients were followed for 24 months after laparoscopic surgery. Those who gave consent but desired no postoperative therapy were assigned to the non-treatment group (n=79). Recurrence, side-effects, degrees of menstrual pain and chronic pelvic pain measured by the Visual Analogue Scale were compared among the three groups: the dienogest, goserelin, and non-treatment groups. No significant difference was observed in the postoperative recurrence rate between the dienogest and goserelin groups. No significant difference was found in the recurrence rate between the goserelin group and non-treatment group; however, a significant difference was found in the recurrence rate between the dienogest group and the non-treatment group (P=0.027). Menstrual pain and chronic pelvic pain were significantly improved in both treatment groups. Side-effects were markedly observed in the goserelin group as compared with the dienogest group. Dienogest is available for prolonged administration of more than 6 months, so it is more useful than goserelin, which is available only for short-term administration.

Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial

How best to treat rising prostate-specific antigen (PSA) concentration after radical prostatectomy is an urgent clinical question. Salvage radiotherapy delays the need for more aggressive treatment such as long-term androgen suppression, but fewer than half of patients benefit from it. We aimed to establish the effect of adding short-term androgen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy. This open-label, multicentre, phase 3, randomised controlled trial, was done in 43 French study centres. We enrolled men (aged ≥18 years) who had received previous treatment for a histologically confirmed adenocarcinoma of the prostate (but no previous androgen deprivation therapy or pelvic radiotherapy), and who had stage pT2, pT3, or pT4a (bladder neck involvement only) in patients who had rising PSA of 0·2 to less than 2·0 μg/L following radical prostatectomy, without evidence of clinical disease. Patients were randomly assigned (1:1) centrally via an interactive web response system to standard salvage radiotherapy (three-dimensional [3D] conformal radiotherapy or intensity modulated radiotherapy, of 66 Gy in 33 fractions 5 days a week for 7 weeks) or radiotherapy plus short-term androgen suppression using 10·8 mg goserelin by subcutaneous injection on the first day of irradiation and 3 months later. Randomisation was stratified using a permuted block method according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00423475. Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. Patients assigned to radiotherapy plus goserelin were significantly more likely than patients in the radiotherapy alone group to be free of biochemical progression or clinical progression at 5 years (80% [95% CI 75-84] vs 62% [57-67]; hazard ratio [HR] 0·50, 95% CI 0·38-0·66; p<0·0001). No additional late adverse events occurred in patients receiving short-term androgen suppression compared with those who received radiotherapy alone. The most frequently occuring acute adverse events related to goserelin were hot flushes, sweating, or both (30 [8%] of 366 patients had a grade 2 or worse event; 30 patients [8%] had hot flushes and five patients [1%] had sweating in the radiotherapy plus goserelin group vs none of 372 patients in the radiotherapy alone group). Three (8%) of 366 patients had grade 3 or worse hot flushes and one patient had grade 3 or worse sweating in the radiotherapy plus goserelin group versus none of 372 patients in the radiotherapy alone group. The most common late adverse events of grade 3 or worse were genitourinary events (29 [8%] in the radiotherapy alone group vs 26 [7%] in the radiotherapy plus goserelin group) and sexual disorders (20 [5%] vs 30 [8%]). No treatment-related deaths occurred. Adding short-term androgen suppression to salvage radiotherapy benefits men who have had radical prostatectomy and whose PSA rises after a postsurgical period when it is undetectable. Radiotherapy combined with short-term androgen suppression could be considered as a reasonable option in this population. French Ministry of Health, AstraZeneca, and La Ligue Contre le Cancer.

Abstract P1-11-01: Depression and anxiety after adjuvant ovarian function suppression in premenopausal breast cancer patients

Abstract Purpose The results of the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT) showed that ovarian function suppression (OFS) in premenopausal early breast cancer patients improves disease control. However, mood swings after OFS is one of the chief complaints to make patients stop undergoing endocrine therapy. Studies about complications of OFS in breast cancer patients are not established well. We designed this randomized controlled trial to evaluate psychological functioning of patients after undergoing adjuvant OFS by goserelin. Patients and Methods We randomly assigned 64 premenopausal women with hormone receptor positive early breast cancer to the tamoxifen or tamoxifen plus goserelin group for a period of 1 year. Participants were screened for depression and generalized anxiety disorder using Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety (HAM-A), Anxiety Sensitivity Index (ASI) and Albany panic and phobia questionnaire (APPQ) at baseline, 6 months and 12 months. Brain-derived Neurotrophic Factor (BDNF) levels were measured, as well. The results were analyzed by using a linear mixed model and a generalized linear mixed model. Results Thirty two patients were distributed in each group, equally. Linear mixed-mixed model analyses revealed that, compared with HAM-A scores of each group at baseline, HAM-A scores at 12 months showed increments (p=0.0078). Among HAM-A questions, Questions for intellectual, sensory and autonomic status were scored significantly high at 12 months (p=0.0018, p=0.0132, p=0.0006). Platelet BDNF levels reported a statistically significant rise at 12 months (p=0.0006). There was no significant time-by-study group effect in all scales. Conclusion Compared with the patients without OFS, patients with Goserelin showed no difference in anxiety or depression scales. Thought the levels of anxiety of each group at 12 months were increased, they do not indicate medical interventions. Patients with increased levels of BDNF at 12 months are expected to have good recovery from anxious and depressive symptoms. Citation Format: Yi HW, Nam SJ, Kim SW, Lee JE, Lee SK, Bae SY, Park S, Paik H-J, Ryu JM. Depression and anxiety after adjuvant ovarian function suppression in premenopausal breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-11-01.

A randomized controlled trial to determine the effect of triptorelin on reduction of prostate volume preradiotherapy compared with standard therapy (goserelin).

30 Background: Hormone therapy in combination with radiotherapy is a curative treatment option for prostate cancer (CaP). Neoadjuvant goserelin is known to reduce prostate gland volume by about 26%, such that radiotherapy treatment volumes are smaller, reducing the risk of damage to bladder and rectum. Triptorelin is 100 times more potent than native LHRH and has a longer half life than both native LHRH and goserelin. This study evaluated the equivalence of cytoreductive efficacy of neoadjuvant triptorelin and goserelin. Methods: Seventy-onepatients with localized CaP who have chosen radical radiotherapy had been randomized by stratified block design, toreceive either triptorelin (n=37) or goserelin (n=34) with bicalutamide cover. Prostate volume was measured at baseline and 14 weeks after start of therapy on transrectal ultrasound (TRUS). PSA, testosterone levels, and EQ5D, QLQ-PR25, QLQ-C30 questionnaires were completed at baseline, 6, 10, and 14 weeks after start of therapy. All the patients had subsequent radical radiotherapy and followed up as per departmental protocol. Changes in TRUS volume and time to castrate levels of testosterone were evaluated. Results: The mean (±S.D) baseline prostate volume in the goserelin and triptorelin groups was 38.1(±12.8) cc and 39.4(±17.5) cc, respectively. The mean (±S.D) reduction in the prostate volume after 14 weeks of goserelin and triptorelin was 36.8(±18.4)% and 32.5(±20.9)%, respectively (p=0.36: Analysis of Covariance). Twenty-nine out of 34 in the goserelin group and 33 out of 37 patients in the triptorelin group achieved castrate levels of testosterone (£0.5nmol/L). The median time to castration was 6.1 (95% CI: 5.8-6.5) and 6.4 (95% CI: 5.9-10.0) weeks for goserelin and triptorelin, respectively (p=0.72: log rank). Conclusions: Goserelin and triptorelin both caused a reduction inprostate volume and achieved castrate levels of testosterone. The cytoreductive efficacy of neoadjuvant triptorelin was equivalent (non-inferior) to that of goserelin. To our knowledge, this is the first reported prospective randomized data demonstrating the equivalence of goserelin and triptorelin in the neoadjuvant setting. Clinical trial information: 2008-007028-25.

Goserelin for Ovarian Protection during Breast-Cancer Adjuvant Chemotherapy

BackgroundOvarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin-releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes.MethodsWe randomly assigned 257 premenopausal women with operable hormone-receptor–negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy-alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival.ResultsAt baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval [CI], 0.09 to 0.97; two-sided P=0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P=0.03); women in the goserelin group also had improved disease-free survival (P=0.04) and overall survival (P=0.05).ConclusionsAlthough missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility. (Funded by the National Cancer Institute and others; POEMS/S0230 ClinicalTrials.gov number, NCT00068601.)

Clinical study on moderate and severe endometriosis operation combined drug therapy

Objective To investigate the effect and severe adverse reactions of goserelin combined with mifepristone after operation for moderate and endometriosis laparoscopic conservative.Methods 68 cases with moderate to severe endometriosis diagnosed after laparoscopic conservative operation were randomly divided into the Gore Sherry Lin group and mifepristone group with 34 cases for 6 months of a course,regular follow-up.Clinical efficacy and adverse reaction for two groups were compared.Results The dysmenorrhea symptoms for two groups of patients have been alleviated,the efficiency rate was above 91％.The recurrence rate of the mifepristone group was higher than the goserelin group (14.71％ vs 2.94％,P ＜ 0.05).The cumulative pregnancy rate of mifepristone group was lower than the goserelin group (20.59％ vs 38.23 ％,P ＜ 0.05) discontinued for 1 years.The liver function damage of the goserelin group was significantly lower than the mifepristone group (2.94％ vs 23.53％,P ＜ 0.05).Conclusion It is more significance for using suppression of ovarian function after laparoscopic conservative operation for severe endometriosis.It can increase the pregnancy rate and decrease the recurrence rate. Key words: Endometriosis; Laparoscopy; Goserelin; Mifepristone

Cost-utility analysis of adjuvant goserelin (Zoladex) and adjuvant chemotherapy in premenopausal women with breast cancer

BackgroundIncreased health care costs have made it incumbent on health-care facilities and physicians to demonstrate both clinical and cost efficacy when recommending treatments. Though studies have examined the cost-effectiveness of adjuvant goserelin with radiotherapy for locally advanced prostate cancer, few have compared the cost-effectiveness of adjuvant goserelin to adjuvant chemotherapy alone in premenopausal breast cancer.MethodsIn this retrospective study at one hospital, the records of 152 patients with stage Ia to IIIa ER + breast cancer who received goserelin or chemotherapy were reviewed. Survival analysis was assessed by the Kaplan-Meier method. Patients were interviewed to evaluate their quality of life using the European Organization for Research and Treatment Quality of Life questionnaire (EORTC-QLQ-C30, version 4.0), and to obtain the utility value by the standard gamble (SG) and visual scale (VS) methods. Total medical cost was assessed from the (National Health Insurance) NHI payer's perspective.ResultsSurvival at 11 years was significantly better in the groserelin group (P < 0.0012). The lifetime lost was lower in the goserelin group (42 months vs. 66 months). The quality adjusted survival (QAS) of patients who received goserelin was longer (122.5 ± 6.3 vs. 112.2 ± 6.7 months). Total expenses of goserelin were more than cyclophosphamide, methotrexate, 5-fluorouracil (CMF) or 5-fluorouracil, epirubicin, cyclophosphamide (FEC) chemotherapy regimes, but less than docetaxel, epirubicin (TE) or docetaxel, epirubicin, cyclophosphamide (TEC) regimes. The quality-adjusted life-year was higher in the goserelin group.ConclusionsGoserelin therapy results in better survival and higher utility-weighted life-years, and is more cost-effective than TC or TEC chemotherapy.

Study on the effects of gonadotropin-releasing hormone analogues in the inhibition of ovarian cancer transplanted tumors and in the protection of ovarian function after chemotherapy on nude mice

To investigate the influence of gonadotropin-releasing hormone (GnRH) analogues on ovarian cancer and ovarian function in vivo. ES-2 cells were cultured and xenotransplanted into 36 nude mice, which were divided into 6 groups: normal saline (NS) group: NS 0.1 ml/day subcutaneous injection, and then NS 0.2 ml/week peritoneal injection; cisplatin (DDP) group: NS 0.1 ml/day subcutaneous injection, and then DDP 5 mg/kg (diluted to 0.2 ml) per week peritoneal injection; goserelin group: 100 µg goserelin (diluted to 0.1 ml) per day subcutaneous injection, and then NS 0.2 ml/week peritoneal injection; goserelin + DDP group: 100 µg goserelin (diluted to 0.1 ml) per day subcutaneous injection, and DDP 5 mg/kg (diluted to 0.2 ml) per week peritoneal injection; cetrorelix group:100 µg cetrorelix (diluted to 0.1 ml) per day subcutaneous injection and NS 0.2 ml/week peritoneal injection; cetrorelix + DDP group: 100 µg cetrorelix (diluted to 0.1 ml) per day subcutaneous injection and DDP 5 mg/kg (diluted to 0.2 ml) per week peritoneal injection. All the peritoneal injection started from subcutaneous injection one week later. To compare the weight of nude mice, the volumes of transplanted tumors, the expression of Ki-67 antigen in transplanted tumors, the estrus, the ratio of atretic follicles, the ratio of primary and preantral follicles, the levels of serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), estradio (E(2)) and progesterone (P) in each group. There were no significant difference in the weight of nude mice among 6 groups (P > 0.05), which on day 29 in NS group was (19.8 ± 2.2) g, DDP group (20.5 ± 1.4) g, gosereline group (19.6 ± 0.9) g, goserelin + DDP group (19.7 ± 1.6) g, cetrorelix group (20.7 ± 2.2) g, and cetrorelix + DDP group (19.0 ± 1.7) g. The tumor volumes of different groups on the 12(th) day: NS group (241 ± 179) mm(3), DDP group (78 ± 20) mm(3), gosereline group (78 ± 55) mm(3), goserelin + DDP group (64 ± 48) mm(3), cetrorelix group (78 ± 64) mm(3), or cetrorelix + DDP group (70 ± 19) mm(3), in which there were significant difference between NS group and the other groups (P < 0.05); and the same result was obtained on day 15, 19, 22, 26 and 29 (P < 0.05). The expression of Ki-67 in NS group was (33 ± 10)%, in which it was higher than those in DDP group 3.5%, goserelin group 8.8%, goserelin + DDP group 1.5%, cetrorelix group (23 ± 11)%, or cetrorelix + DDP group (8 ± 6)% (P < 0.05). The ratio of primary and preantral follicles in goserelin group was (71.5 ± 8.1)%, in goserelin + DDP group was (62.4 ± 4.1)%, in cetrorelix group was (71.2 ± 7.4)%, and in cetrorelix + DDP group was (63.8 ± 3.1)%, in which they were much higher than that in DDP group (47.0 ± 4.8)% (P < 0.05). The level of AMH in goserelin group was (98 ± 27) ng/ml, which was much higher than that in NS group (66.2 ± 17.4) ng/ml (P < 0.05), while there were no difference in the levels of FSH, E(2) or P among different groups (P > 0.05). GnRH analogues could inhibit the growth of transplanted tumors in nude mice, meanwhile increase the secretion of AMH, decrease the frequencies and prolong the lasting time of estrus, decrease the ratio of atretic follicles, raise the ratio of primary and preantral follicles, which may be protect the ovarian function of nude mice.