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Tommy Fornander - One of the best experts on this subject based on the ideXlab platform.
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interaction between Goserelin and tamoxifen in a prospective randomised clinical trial of adjuvant endocrine therapy in premenopausal breast cancer
Breast Cancer Research and Treatment, 2011Co-Authors: Asgerdur Sverrisdottir, Hemming Johansson, Ulla Johansson, Jonas Bergh, S Rotstein, L E Rutqvist, Tommy FornanderAbstract:Ovarian ablation improves survival in premenopausal early breast cancer, but the potential added value by luteinizing hormone-releasing hormone (LHRH) agonists to tamoxifen is still not clear. The purpose of our study is to examine the efficacy of the LHRH agonist Goserelin for adjuvant therapy of premenopausal breast cancer, the role of interaction between Goserelin and tamoxifen and the impact of estrogen receptor (ER) content. A total of 927 patients were included in the Stockholm part of the Zoladex in Premenopausal Patients (ZIPP) trial. They were randomly allocated in a 2 × 2 factorial study design to Goserelin, tamoxifen, the combination of Goserelin and tamoxifen or no endocrine therapy for 2 years, with or without chemotherapy. This is formally not a preplanned subset analysis presenting the end point first event. In this Stockholm sub-study, at a median follow-up of 12.3 years, Goserelin reduced the risk of first event by 32% (P = 0.005) in the absence of tamoxifen, and tamoxifen reduced the risk by 27% (P = 0.018) in the absence of Goserelin. The combined Goserelin and tamoxifen treatment reduced the risk by 24% (P = 0.021) compared with no endocrine treatment. In highly ER-positive tumours, there were 29% fewer events among Goserelin treated (P = 0.044) and a trend towards greater risk reduction depending on the level of ER content. The greatest risk reduction from Goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, P = 0.007). In conclusion, Goserelin as well as tamoxifen reduces the risk of recurrence in endocrine responsive premenopausal breast cancer. Women with strongly ER-positive tumours may benefit more from Goserelin treatment. The combination of Goserelin and tamoxifen is not superior to either modality alone. With the limitations of a subset trial, these data have to be interpreted cautiously.
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abstract s1 5 interaction between Goserelin and tamoxifen in a controlled clinical trial of adjuvant endocrine therapy in premenopausal breast cancer
Cancer Research, 2010Co-Authors: Asgerdur Sverrisdottir, Hemming Johansson, Ulla Johansson, Jonas Bergh, S Rotstein, L E Rutqvist, Tommy FornanderAbstract:Background: Ovarian ablation improves survival in premenopausal women with early breast cancer, but the potential added value by luteinizing hormone-releasing hormone agonists (LHRH-a) to tamoxifen, is still not clear. There has been lack of data reported separately for patients who underwent randomization to both LHRH-a and tamoxifen. Patients and Methods: In Stockholm, 927 patients assigned to the Zoladex in Premenopausal Patients (ZIPP) trial, were included in a 2 x 2 factorial randomization to Goserelin (3.6 mg subcutaneously, q 28d), tamoxifen (40 mg daily), the combination of Goserelin and tamoxifen or no endocrine therapy for two years, with or without chemo-and/or radiotherapy. The trial was designed to examine the effect of Goserelin and the role of interaction between Goserelin and tamoxifen in adjuvant therapy of premenopausal breast cancer. We examined as well, the impact of different estrogen receptor (ER) content on treatment effect. The definition of first event was breast cancer recurrence, contra lateral breast cancer or death. The ER content was determined by isoelectric focusing on polyacrylamide gel and receptor values normalized to DNA content. Results: After a median follow up of 12.3 years, Goserelin reduced the risk of first event by 32% (p=0.005) in the absence of tamoxifen and tamoxifen reduced the risk by 27% (p=0.018) in the absence of Goserelin. The combined Goserelin and tamoxifen treatment reduced the risk by 24% (p=0.021) and there was a significant interaction between Goserelin and tamoxifen (p=0.025). In highly ER positive tumours, there were 29% fewer events among Goserelin treated (p=0.044) and a trend towards greater risk reduction depending on the level of ER content. The greatest risk reduction from Goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, p=0.007). For tamoxifen, there was not a significant risk reduction at different ER levels, but there was a trend towards interaction between Goserelin and tamoxifen effect among the highly ER positive (p=0.076). Discussion: In this strictly randomized cohort of endocrine responsive premenopausal breast cancer, Goserelin as well as tamoxifen, reduces the risk of recurrence. However, the combination of Goserelin and tamoxifen is not superior to either modality alone. The effect of Goserelin seems to be modified by ER levels, whereas tamoxifen effect is not. Women with strongly estrogen receptor positive tumours may benefit more from Goserelin treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S1-5.
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long term effectiveness of adjuvant Goserelin in premenopausal women with early breast cancer
Journal of the National Cancer Institute, 2009Co-Authors: Allan Hackshaw, Ulla Johansson, Tommy Fornander, Bo Nordenskjold, Antonio Nicolucci, Michael J Baum, Kathryn Monson, Sharon Forsyth, Krystyna Reczko, Helena FohlinAbstract:Systematic reviews have found that luteinizing hormone-releasing hormone (LHRH) agonists are effective in treating premenopausal women with early breast cancer.We conducted long-term follow-up (median 12 years) of 2706 women in the Zoladex In Premenopausal Patients (ZIPP), which evaluated the LHRH agonist Goserelin (3.6 mg injection every 4 weeks) and tamoxifen (20 or 40 mg daily), given for 2 years. Women were randomly assigned to receive each therapy alone, both, or neither, after primary therapy (surgery with or without radiotherapy/chemotherapy). Hazard ratios and absolute risk differences were used to assess the effect of Goserelin treatment on event-free survival (breast cancer recurrence, new tumor or death), overall survival, risk of recurrence of breast cancer, and risk of dying from breast cancer, in the presence or absence of tamoxifen.Fifteen years after the initiation of treatment, for every 100 women not given tamoxifen, there were 13.9 (95% confidence interval [CI] = 17.5 to 19.4) fewer events among those who were treated with Goserelin compared with those who were not treated with Goserelin. However, among women who did take tamoxifen, there were 2.8 fewer events (95% CI = 7.7 fewer to 2.0 more) per 100 women treated with Goserelin compared with those not treated with Goserelin. The risk of dying from breast cancer was also reduced at 15 years: For every 100 women given Goserelin, the number of breast cancer deaths was lower by 2.6 (95% CI = 6.6 fewer to 2.1 more) and 8.5 (95% CI = 2.2 to 13.7) in those who did and did not take tamoxifen, respectively, although in the former group the difference was not statistically significant.Two years of Goserelin treatment was as effective as 2 years of tamoxifen treatment 15 years after starting therapy. In women who did not take tamoxifen, there was a large benefit of Goserelin treatment on survival and recurrence, and in women who did take tamoxifen, there was a marginal potential benefit on these outcomes when Goserelin was added.
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adjuvant Goserelin and ovarian preservation in chemotherapy treated patients with early breast cancer results from a randomized trial
Breast Cancer Research and Treatment, 2009Co-Authors: Asgerdur Sverrisdottir, M Nystedt, H Johansson, Tommy FornanderAbstract:The purpose of this randomized study was to examine if Goserelin concomitant to CMF-chemotherapy as adjuvant treatment for premenopausal breast cancer, protects the ovaries from premature failure. A total of 285 premenopausal breast cancer patients, in a randomized adjuvant trial (Zoladex in premenopausal patients (ZIPP)), were assigned to a study on ovarian function. Node positive patients were assigned to CMF-(cyclophosphamide, methotrexate and 5-fluorouracil) chemotherapy in addition to endocrine therapy. All patients were randomly assigned to receive 2 years of Goserelin, Goserelin plus tamoxifen, tamoxifen alone or no endocrine treatment. We studied, if menses were affected in the treatment groups, up to 36 months after randomization. One year after completed CMF- and endocrine therapy, 36% of the women in the Goserelin group reported menses, compared to 7% in the Goserelin plus tamoxifen group, 13% in the tamoxifen group and 10% of the controls. Among women treated with Goserelin, there was a statistically significant increase in the proportion of menstruating women, 1 year after completed treatment compared to at 24 months of treatment (P = 0.006), in contrast to all other treatment groups, who were unchanged or more often amenorrheic. In our study, there is some evidence of protective effect of Goserelin on ovarian function in CMF treated women. This effect was not observed in the combined tamoxifen and Goserelin treatment.
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adjuvant Goserelin in pre menopausal patients with early breast cancer results from the zipp study
European Journal of Cancer, 2006Co-Authors: Michael Baum, Tommy Fornander, Allan Hackshaw, J Houghton, Bo Nordenskjold, Antonio Nicolucci, R SainsburyAbstract:The Zoladex In Pre-menopausal Patients (ZIPP) study was designed to determine whether addition of Goserelin (‘Zoladex’) and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer. A combined analysis of four randomised trials using a core protocol was performed. Patients (n = 2710) were randomised into a 2 × 2 factorial trial based on Goserelin and tamoxifen (n = 1800) or randomised to receive Goserelin or not (n = 910; some received elective tamoxifen) for 2 years. The analysis presented here compares women who did (n = 1354) or did not (n = 1356) receive Goserelin. After a median follow-up of 5.5 years, Goserelin provided a significant benefit for event-free survival (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.69, 0.92; P = 0.002) and overall survival (HR 0.81; 95% CI 0.67, 0.99; P = 0.038). Goserelin was well tolerated. These data show that the addition of Goserelin to standard adjuvant therapy is more effective than standard therapy alone in pre-menopausal women with early breast cancer.
W Jonat - One of the best experts on this subject based on the ideXlab platform.
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Goserelin (Zoladex)--its role in early breast cancer in pre- and perimenopausal women.
British journal of cancer, 2020Co-Authors: W JonatAbstract:Current standard adjuvant therapies for premenopausal women with early breast cancer include ovarian ablation by surgery or irradiation, chemotherapy and tamoxifen. The value of ovarian ablation in prolonging the survival of premenopausal patients with early breast cancer was clearly established by the analyses performed by the Early Breast Cancer Trialists' Collaborative Group in 1996. More recently, the value of ovarian suppression using the luteinizing hormone releasing hormone analogue Goserelin as adjuvant therapy in pre-/perimenopausal women with early breast cancer has been confirmed in a series of studies involving over 8000 patients. The results from these studies provide evidence that Goserelin, alone or in combination with tamoxifen, is at least as effective as cytotoxic chemotherapy in patients with hormone receptor-positive tumours and is effective when used after adjuvant chemotherapy. The use of Goserelin in the management of early breast cancer presents an option which can avoid the side-effects experienced with cytotoxic chemotherapy and may offer unique benefits to premenopausal patients. The consolidation of these emerging results should help in defining the optimal role for Goserelin in pre-/perimenopausal patients with early breast cancer.
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cmf versus Goserelin as adjuvant therapy for node negative hormone receptor positive breast cancer in premenopausal patients a randomised trial gabg trial iv a 93
European Journal of Cancer, 2006Co-Authors: Gunter Von Minckwitz, W Jonat, Wolfgang Eiermann, Erika Graf, M Geberth, B Conrad, K Brunnert, Bernd Gerber, S Vescia, Jorg WollertAbstract:Abstract Gonadotrophin-releasing hormone analogues were investigated as adjuvant treatment for patients with node-negative, hormone-sensitive, premenopausal breast cancer. Patients were randomised to either three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy ( n = 378) or Goserelin every 28 d for 2 years ( n = 393). During a median follow-up of 4.9 years, 123 events were observed. The first-failure event of CMF versus Goserelin, respectively, was ipsilateral locoregional recurrence (18 versus 20), contralateral breast cancer (7 versus 6), distant failure (35 versus 24) and death without recurrence (2 versus 2). Forty-two (23 versus 19) deaths of any cause occurred. The estimated adjusted hazard ratio for Goserelin versus CMF (intention-to-treat analysis) was 0.79 (95% CI = 0.54–1.14; P = 0.19). It is concluded that medical ovarian ablation with Goserelin represents a valid option for premenopausal patients with node-negative breast cancer.
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survival analyses from the zebra study Goserelin zoladex versus cmf in premenopausal women with node positive breast cancer
European Journal of Cancer, 2003Co-Authors: M Kaufmann, Ignac Fogelman, Martin Schumacher, W Jonat, R W Blamey, Jack Cuzick, M Namer, J C J M De Haes, W SauerbreiAbstract:The Zoladex Early Breast Cancer Research Association (ZEBRA) trial compared the efficacy and tolerability of Goserelin (Zoladex) with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy in pre-/perimenopausal women with node-positive early breast cancer. The results of disease-free survival (DFS) analyses have already been published. Here we present an update including data on overall survival (OS) from the ZEBRA trial at a median follow-up of 7.3 years. In patients with oestrogen receptor (ER)-positive tumours, non-inferiority of Goserelin versus CMF for OS was shown; Goserelin was again shown to be equivalent to CMF for DFS. This updated analysis has demonstrated that the two treatments are also equivalent for distant disease-free survival (DDFS). In patients with ER-negative disease, Goserelin was inferior to CMF for DFS, DDFS and OS. This follow-up analysis confirms the previously reported outcomes from the ZEBRA trial and demonstrates that Goserelin offers an effective alternative to CMF chemotherapy for adjuvant therapy of premenopausal patients with ER-positive, node-positive early breast cancer.
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Goserelin versus cyclophosphamide methotrexate and fluorouracil as adjuvant therapy in premenopausal patients with node positive breast cancer the zoladex early breast cancer research association study
Journal of Clinical Oncology, 2002Co-Authors: W Jonat, Ignac Fogelman, W Sauerbrei, M Kaufmann, R W Blamey, Jack Cuzick, M Namer, J C J M De Haes, A De Matteis, Alan L StewartAbstract:PURPOSE: Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause. PATIENTS AND METHODS: The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of Goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer. RESULTS: Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P = .0016). In ER-positive patients (approximately 74%), Goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, Goserelin was inferior to CMF for DFS (HR, ...
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Goserelin (Zoladex ™) – its role in early breast cancer in pre- and perimenopausal women
British Journal of Cancer, 2001Co-Authors: W JonatAbstract:Current standard adjuvant therapies for premenopausal women with early breast cancer include ovarian ablation by surgery or irradiation, chemotherapy and tamoxifen. The value of ovarian ablation in prolonging the survival of premenopausal patients with early breast cancer was clearly established by the analyses performed by the Early Breast Cancer Trialists’ Collaborative Group in 1996. More recently, the value of ovarian suppression using the luteinizing hormone releasing hormone analogue Goserelin as adjuvant therapy in pre-/perimenopausal women with early breast cancer has been confirmed in a series of studies involving over 8000 patients. The results from these studies provide evidence that Goserelin, alone or in combination with tamoxifen, is at least as effective as cytotoxic chemotherapy in patients with hormone receptor-positive tumours and is effective when used after adjuvant chemotherapy. The use of Goserelin in the management of early breast cancer presents an option which can avoid the side-effects experienced with cytotoxic chemotherapy and may offer unique benefits to premenopausal patients. The consolidation of these emerging results should help in defining the optimal role for Goserelin in pre-/perimenopausal patients with early breast cancer. © 2001 Cancer Research Campaign
Jacques Donnez - One of the best experts on this subject based on the ideXlab platform.
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a randomized placebo controlled dose ranging trial comparing fulvestrant with Goserelin in premenopausal patients with uterine fibroids awaiting hysterectomy
Fertility and Sterility, 2003Co-Authors: Jacques Donnez, Blas Hervais Vivancos, Milan Kudela, Alain Audebert, Pascale JadoulAbstract:OBJECTIVE: To compare the use of a new antiestrogen fulvestrant with Goserelin in reducing uterine fibroid growth before hysterectomy. DESIGN: An international, multicenter, randomized, placebo-controlled study. SETTING: Departments of obstetrics and gynecology. PATIENT(S): Premenopausal women (n = 307) diagnosed with uterine fibroids requiring hysterectomy. INTERVENTION(S): Over a 12-week period, patients received fulvestrant (50 mg, 125 mg, or 250 mg) as an i.m. injection, Goserelin (3.6 mg) as a s.c. injection, or an injection-matched placebo once every 4 weeks. Patients underwent a hysterectomy at week 13. MAIN OUTCOME MEASURES: Efficacy endpoints included changes in fibroid growth, endometrial thickness, and uterine volume. The excretion of urinary markers of bone resorption was also examined. RESULT(S): Goserelin significantly reduced fibroid growth and endometrial thickness compared with placebos. Fulvestrant did not significantly alter fibroid volume or endometrial thickness or change endpoints such as endometrial histology or vaginal bleeding. Fulvestrant was associated with fewer postmenopause-related adverse events than Goserelin. Goserelin, but not fulvestrant, significantly increased markers of bone resorption. CONCLUSION(S): At doses equivalent to those used for the treatment of breast cancer in postmenopausal women, fulvestrant did not significantly inhibit fibroid growth and, of particular note, did not lead to bone resorption.
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Goserelin acetate zoladex plus endometrial ablation for dysfunctional uterine bleeding a 3 year follow up evaluation
Fertility and Sterility, 2001Co-Authors: Jacques Donnez, Georges Vilos, Michael J Gannon, R Maheux, M H Emanuel, O IstreAbstract:OBJECTIVE: To report the results of a 3-year follow-up evaluation of a trial comparing Goserelin acetate depot injections with sham injections before endometrial ablation for the treatment of dysfunctional uterine bleeding (DUB). DESIGN: Prospective, randomized, double-blind, parallel-group study. SETTING: Thirty-seven centers in 12 countries. PATIENT(S): Three-hundred and fifty-eight premenopausal women aged over 30 years with DUB. INTERVENTION(S): Goserelin acetate (3.6 mg depot) every 28 days for 8 weeks, or sham depot every 28 days for 8 weeks, with endometrial ablation 6 weeks +/- 3 days after the first depot injection (i.e., when the endometrium is at its thinnest). The follow-up continued for 3 years. MAIN OUTCOME MEASURE(S): At the 3-year follow-up, bleeding in the previous 3 months and need for surgical intervention were recorded. RESULT(S): At 3 years, amenorrhea rates were 21% in the Goserelin acetate group and 14% in the control group (estimated odds ratio, 1.8; 95% CI, 0.98-3.25; P=.0571). The surgical intervention rate (since the original procedure) was low and did not differ significantly between groups. For hysterectomy, it was 21% for the Goserelin acetate group and 15% for the control group. For repeat ablations, it was 5.6% for the Goserelin acetate group and 2.1% for the control group. CONCLUSION(S): Prethinning with Goserelin acetate before endometrial ablation resulted in higher long-term amenorrhea rates than ablation without prethinning.
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Goserelin acetate zoladex plus endometrial ablation for dysfunctional uterine bleeding a large randomized double blind study
Fertility and Sterility, 1997Co-Authors: Jacques Donnez, Georges Vilos, Michael J Gannon, Soren Stampesorensen, Ingemar Klinte, Robert M MillerAbstract:OBJECTIVE: To confirm the advantages of Goserelin prior to endometrial ablation for the treatment of dysfunctional uterine bleeding. DESIGN: Multicenter, prospective, randomized, double-blind study. PATIENT(S): Cycling premenopausal women with dysfunctional uterine bleeding. TREATMENT: Patients were randomized to Goserelin or placebo (sham depot) once monthly for 2 months prior to endometrial ablation. Treatment was timed to allow surgery 6 weeks later on day 7 of the menstrual cycle. MAIN OUTCOME MEASURE(S): Amenorrhea rates, endometrial histology and thickness, pain and blood loss scores, and surgical parameters. RESULT(S): At 24 weeks after surgery, significantly more Goserelin than placebo patients experienced amenorrhea (40% versus 26%). Blood loss was reduced from baseline, but not different between the groups. At surgery, mean endometrial thickness was 1.6 mm and 3.4 mm for the Goserelin and placebo groups, respectively, with significantly more atrophic glands and stroma in the Goserelin group. Surgery was significantly shorter (by 22%) and easier in the Goserelin than in the placebo group, with a significantly lower median fluid absorption in the Goserelin groups. In both groups, pain scores were reduced patient satisfaction was high (> 92%), and re-intervention rate was low (2.8%). CONCLUSION(S): Goserelin in combination with endometrial ablation was superior to endometrial ablation alone for the treatment of dysfunctional uterine bleeding.
R N Brogden - One of the best experts on this subject based on the ideXlab platform.
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Goserelin a review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in benign gynaecological disorders
Drugs, 1996Co-Authors: Caroline M Perry, R N BrogdenAbstract:: Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue which, during continuous administration, down-regulates the pituitary-ovarian gonadal axis and reduces levels of the gonadotrophins, luteinising hormone and follicle-stimulating hormone. In women, this results in suppression of ovarian steroidogenesis and a decline in estrogen to levels similar to those observed after menopause or following surgical oophorectomy. Thus, Goserelin has a useful role in the management of some benign estrogen-dependent gynaecological disorders. Goserelin is available as a biodegradable sustained release depot 3.6mg injection which is administered every 28 days. In women with endometriosis, monthly injections of depot Goserelin were effective in achieving resolution of endometriotic implants and in improving pelvic symptoms, including pain and dyspareunia. Randomised clinical comparisons of depot Goserelin with danazol indicate that Goserelin is at least as effective as danazol and is better tolerated in the treatment of endometriosis. In the management of uterine leiomyomata (fibroids), Goserelin depot injections reduce uterine size and the size of uterine leiomyomata, with maximum clinical benefit achieved approximately 3 to 4 months after initiation of treatment. When used as an adjunctive pretreatment for women undergoing surgical removal of uterine leiomyomata, Goserelin was associated with technically easier surgical procedures, reduced intraoperative blood loss and reduced transfusion requirements around the time of surgery. As an alternative to surgery, therapeutic use of Goserelin is limited by the rapid regrowth of leiomyomata following cessation of treatment. However, Goserelin may be a useful treatment for women approaching menopause, in whom uterine leiomyomata shrink naturally as endogenous estrogen levels decline. In women with dysfunctional uterine bleeding, treatment with depot Goserelin before surgery facilitates resection and ablative procedures by suppressing endometrial growth and thinning the endometrial mucosa. Goserelin is also an effective alternative to surgery in this patient group. As adjuvant therapy for women undergoing assisted reproduction procedures, Goserelin is associated with reduced cycle cancellation rates and with an increase in the rate of oocyte retrieval. The tolerability profile of Goserelin is characterised by adverse effects typical of hypoestrogenism, including hot flushes, loss of libido and loss of bone mineral density. However, concomitant 'add-back' hormone replacement therapy appears to effectively reduce these hypoestrogenic symptoms. In summary, the availability of depot Goserelin has broadened the spectrum of effective treatments for benign estrogen-dependent gynaecological disorders. As Goserelin is effective as a sustained release depot formulation suitable for administration on a monthly basis, it is also a convenient and practical treatment choice.
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Goserelin a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in prostate cancer
Drugs & Aging, 1993Co-Authors: R N Brogden, Diana FauldsAbstract:: Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue which during long term administration reduces circulating levels of gonadotrophins (luteinising hormone and follicle stimulating hormone) and sex hormones. Goserelin is administered subcutaneously as a biodegradable depot formulation incorporating 3.6mg of the drug, which is released continuously over 4 weeks. In men with untreated advanced prostate cancer, monthly Goserelin 3.6mg has been confirmed as similar in efficacy to surgical castration and diethylstilbestrol (stilboestrol) 3mg daily taken orally. Goserelin is better tolerated than diethylstilbestrol and appears to have a more favourable effect on quality of life than surgical castration. Treatment of prostate cancer with a combination of Goserelin and an antiandrogen remains controversial as a result of inconsistent findings, despite extended data from a large trial which indicated an advantage for the combined regimen over surgical castration with respect to duration of time to progression and survival. Combination therapy also minimises the initial increase in signs and symptoms (disease flare) that occurs in up to 4% of patients at the beginning of treatment with a GnRH analogue. Surgical castration remains the treatment of choice in patients at risk of metastatic compression of the spinal cord or ureteric obstruction. However, Goserelin is an effective alternative to surgery, or estrogen therapy, in men with previously untreated advanced prostate cancer. Goserelin seems to be preferred to surgery by the majority of patients given a choice of treatment, and importantly in a palliative care situation where there are no survival advantages for treatment alternatives, it appears to have a more beneficial effect on the quality of life than surgery.
V Khoo - One of the best experts on this subject based on the ideXlab platform.
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neoadjuvant androgen deprivation therapy for prostate volume reduction lower urinary tract symptom relief and quality of life improvement in men with intermediate to high risk prostate cancer a randomised non inferiority trial of degarelix versus gos
Clinical Oncology, 2013Co-Authors: Malcom Mason, Maldonado X Pijoan, C Steidle, S Guerif, Thomas Wiegel, E Van Der Meulen, Peter Bergqvist, V KhooAbstract:Abstract Aims The treatment of intermediate- to high-risk prostate cancer with radical radiotherapy is usually in combination with neoadjuvant androgen deprivation therapy. The aim of the present trial was to investigate whether degarelix achieves comparable efficacy with that of Goserelin plus bicalutamide as neoadjuvant therapy before radiotherapy. Materials and methods The study was a randomised, parallel-arm, active-controlled, open-label trial in 244 men with a UICC prostate cancer TNM category T2b–T4, N0, M0, Gleason score ≥7, or prostate-specific antigen ≥10 ng/ml and a total prostate volume >30 ml, who were scheduled to undergo radical radiotherapy and in whom neoadjuvant androgen deprivation therapy was indicated. Eligible patients received treatment with either monthly degarelix (240/80 mg) or Goserelin (3.6 mg) for 12 weeks, the latter patients also receiving bicalutamide (50 mg) for 17 days initially. The primary efficacy measure was the mean percentage reduction in total prostate volume from baseline at week 12 measured by transrectal ultrasound. The severity and relief of lower urinary tract symptoms were assessed by the International Prostate Symptom Score questionnaire. Quality of life was assessed by the eighth question of the International Prostate Symptom Score. About 50% of the patients had moderate to severe lower urinary tract symptoms at baseline. Results The total prostate volume decreased significantly from baseline to week 12 in both treatment groups, reaching −36.0 ± 14.5% in degarelix-treated patients and −35.3 ± 16.7% in Goserelin-treated patients (adjusted difference: −0.3%; 95% confidence interval: −4.74; 4.14%). At the end of the therapy, more degarelix- than Goserelin-treated patients reported International Prostate Symptom Score decreases of ≥3 points (37% versus 27%, P = 0.21). In addition, in patients with a baseline International Prostate Symptom Score of ≥13, the magnitude of the decrease was larger in degarelix- ( n = 53) versus Goserelin-treated patients ( n = 17) (6.04 versus 3.41, P = 0.06). Conclusions The efficacy of degarelix in terms of prostate shrinkage is non-inferior to that of Goserelin plus bicalutamide. The added benefits of degarelix in terms of more pronounced lower urinary tract symptom relief in symptomatic patients could be the reflection of differences in the direct effects on extra-pituitary receptors in the lower urinary tract [Clinicaltrials.gov ID: NCT00833248].
