Zoladex scientific update |
|
 |
|
Radiat Oncol. 2007 Aug 26;2:31.
Hermann RM, Schwarten D, Fister S, Grundker C, Rave-Frank M, Nitsche M, Hille A, Thelen P, Schmidberger H, Christiansen H.
Department of Radiotherapy, University hospital, Robert-Koch-Str, 40, 37075 Göttingen, Germany.
No supra-additive effects of goserelin and radiotherapy on clonogenic survival of prostate carcinoma cells in vitro.
ABSTRACT: BACKGROUND: Oncological results of radiotherapy for locally advanced prostate cancer (PC) are significantly improved by simultaneous application of LHRH analoga (e.g. goserelin). As 85% of PC express LHRH receptors, we investigated the interaction of goserelin incubation with radiotherapy under androgen-deprived conditions in vitro. METHODS: LNCaP and PC-3 cells were stained for LHRH receptors. Downstream the LHRH receptor, changes in protein expression of c-fos, phosphorylated p38 and phosphorylated ERK1/2 were analyzed by means of Western blotting after incubation with goserelin and irradiation with 4 Gy. Both cell lines were incubated with different concentrations of goserelin in hormone-free medium. 12 h later cells were irradiated (0 - 4 Gy) and after 12 h goserelin was withdrawn. Endpoints were clonogenic survival and cell viability (12 h, 36 h and 60 h after irradiation). RESULTS: Both tested cell lines expressed LHRH-receptors. Changes in protein expression demonstrated the functional activity of goserelin in the tested cell lines. Neither in LNCaP nor in PC-3 any significant effects of additional goserelin incubation on clonogenic survival or cell viability for all tested concentrations in comparison to radiation alone were seen. CONCLUSION: The clinically observed increase in tumor control after combination of goserelin with radiotherapy in PC cannot be attributed to an increase in radiosensitivity of PC cells by goserelin in vitro.
Breast Cancer Res Treat. 2008 Aug;110(3):411-6.
Urruticoechea A, Arnedos M, Walsh G, Dowsett M, Smith IE.
Institut Catala d'Oncologia, Hospital Duran i Reynalds, Gran Via km 2.7. L'Hospitalet de Llobregat, Barcelona, Spain.
Ovarian protection with goserelin during adjuvant chemotherapy for pre-menopausal women with early breast cancer (EBC).
PURPOSE: Ovarian failure and infertility following adjuvant chemotherapy for early breast cancer are major concerns for some young women. Techniques for oocyte harvesting are associated with delay in starting treatment, potentially undesirable estrogen stimulation and a relatively low success rate. We report an audit of our experience with the luteinising hormone-releasing hormone agonist, goserelin, to achieve transient ovarian suppression during chemotherapy as a means of preserving ovarian function. PATIENT AND METHODS: Pre-menopausal women were offered goserelin 3.6 mg by subcutaneous injection every 28 days during chemotherapy, starting 0-14 days prior to treatment. The primary end-point was recovery of menstruation. Serum luteinising hormone, follicle stimulating hormone and oestradiol were measured at recovery of menstruation or at first year follow-up if amenorrhoea persisted. Subsequent pregnancies were recorded. RESULTS: Fifty-one evaluable women were audited. Amenorrhoea occurred in all but one. All received combination anthracycline-containing chemotherapy regimens with a mean cumulative cyclophosphamide dose of 3.9 g/m(2). Forty-five (90%) recovered menstruation during the first year of follow-up; mean time to recovery 5 months. Eight pregnancies in 10 women attempting this so far. CONCLUSION: Using goserelin concurrently with chemotherapy is associated with a high rate of ovarian function preservation.
Cancer. 2007 Dec 1;110(11):2448-56.
Levine D, Park K, Juretzka M, Esch J, Hensley M, Aghajanian C, Lewin S, Konner J, Derosa F, Spriggs D, Iasonos A, Sabbatini P.
Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission.
BACKGROUND: The current study was conducted to determine the effect of goserelin and bicalutamide on progression-free survival (PFS) in patients with epithelial ovarian cancer who were in second or greater complete disease remission. METHODS: Patients received bicalutamide at a dose of 50 mg orally daily and goserelin at a dose of 3.6 mg subcutaneously every 4 weeks. CA 125 was obtained monthly, with computed tomography performed every 3 months. Correlative studies included serum luteinizing hormone, follicle-stimulating hormone, vascular endothelial growth factor, free testosterone, and androstenedione and the germline polymorphisms CYP19A1 and androgen receptor. RESULTS: Between October of 2000 and October of 2002, 35 patients were enrolled. Three patients (9%) received therapy at the time of first disease remission and were removed from the study, and 1 patient (3%) was removed for liver function test abnormalities. The most frequent toxicities were grade 1 alkaline phosphatase (54%), fatigue (57%), and hot flashes (42%) based on the National Cancer Institute common toxicity scale, version 2.0. The PFS for patients receiving protocol therapy in second disease remission (21 patients) was 11.4 months (95% confidence interval [95% CI], 10.2-12.6 months). The PFS for patients receiving protocol therapy in third or fourth disease remission (11 patients) was 11.9 months (95% CI, 10.8-14.1 months). The percentage of patients remaining in second disease remission at given times are: 100% at 3 months, 100% at 6 months, 72% at 9 months, 47% at 12 months, 28% at 15 months, 22% at 18 months, 19% at 21 months, and 13% at 24 months. There were no associations noted between androgen receptor repeat number, genotype, allelotype, or haplotypes and PFS. CONCLUSIONS: The use of goserelin and bicalutamide did not appear to prolong PFS in patients with epithelial ovarian cancer in second or greater complete disease remission. The number of patients in disease remission at given time points may serve as a clinical trial endpoint for future studies of consolidation therapy.
Clin Ther. 2007 Aug;29(8):1682-91.
Muneyyirci-Delale O, Richard-Davis G, Morris T, Armstrong J.
State University of New York Health Center at Brooklyn, Brooklyn, New York 11203-2098, USA. Ozgul.
Goserelin acetate 10.8 mg plus iron versus iron monotherapy prior to surgery in premenopausal women with iron-deficiency anemia due to uterine leiomyomas: results from a Phase III, randomized, multicenter, double-blind, controlled trial.
BACKGROUND: Women with symptomatic uterine leiomyomas (fibroids) may have iron-deficiency anemia (IDA); therefore, surgery places them at risk of blood-borne morbidity from perioperative transfusions. Such women might benefit from a preoperative treatment that restores hematologic normality and alleviates fibroid symptoms. OBJECTIVE: The purpose of this study was to examine the effects of a single preoperative depot injection of goserelin acetate plus iron treatment compared with iron monotherapy, in premenopausal women with IDA due to uterine leiomyomas. METHODS: This Phase III, randomized, multicenter, double-blind, controlled trial (12 weeks of treatment plus a 24-week follow-up period) was conducted from October 1997 to August 1999. Patients received an injection of goserelin acetate 10.8 mg (3-month formulation) or a sham, with both groups receiving PO iron (ferrous sulfate) 325-mg tablets TID during the 12-week treatment period. Surgery (hysterectomy or myomectomy) was planned for week 12. Hemoglobin (Hb) level, symptoms of uterine leiomyomas, requirement for blood transfusion throughout, ability to donate blood for autologous transfusion, and leiomyoma and uterine volume were assessed for efficacy. The tolerability assessment included bone mineral density measurements and subjective symptomatology (ie, menstrual bleeding [uterine hemorrhage], fatigue, pelvic pain, and pelvic pressure). RESULTS: A total of 110 women received treatment (n = 54, goserelin acetate 10.8 mg; n = 56, sham). The majority of patients (69.1%) were black and the mean age at study entry was 39.9 years, with a mean weight of 80.1 kg. At approximately 12 weeks, Hb levels were significantly higher in the goserelin group compared with the sham group (difference of least squares mean, 1.17 g/dL; 95% CI, 0.68-1.66; P < 0.001), and significantly more patients in the goserelin group had an increase in Hb concentration of >or=2 g/dL (odds ratio 6.36; 95% CI, 2.00-20.18; P < 0.001). A nonsignificant decrease in both uterine and leiomyoma volume was experienced by patients who administered goserelin compared with increases in the sham group. Uterine hemorrhage was also experienced numerically less often by goserelin-treated patients compared with those given the sham injection (9.3% vs 28.6%, respectively). One or more adverse events (AEs) were reported by 89% of patients in each treatment group. Goserelin acetate 10.8 mg was generally well tolerated by patients, with no serious drug-related AEs reported during this 36-week trial. CONCLUSION: A single, preoperative injection of goserelin acetate 10.8 mg in addition to PO iron 325 mg TID was associated with improved Hb levels in these premenopausal women with IDA due to uterine leiomyomas.
Int J Gynaecol Obstet. 2008 May;101(2):178-83.
Lim SS, Sockalingam JK, Tan PC.
Department of Obstetrics and Gynecology, University of Malaya, Kuala Lumpur, Malaysia.
Goserelin versus leuprolide before hysterectomy for uterine fibroids.
OBJECTIVE: To compare goserelin and leuprolide given before hysterectomy for symptomatic large fibroid uteri. METHODS: A randomized study of 66 premenopausal women with fibroid uteri at least 14 weeks of gestation in a gravid uterus. Women were randomized to receive either subcutaneous depot 3.6 mg goserelin or 3.75 mg leuprolide every 4 weeks for a total of 3 doses. Hysterectomy was performed within 1 month of the last dose. RESULTS: A total of 34 women randomized to the goserelin group and 31 women to the leuprolide group were available for analysis. Preoperative hemoglobin level (P=0.89), operative blood loss (P=0.72), and operating time (P=0.39) were not different between the 2 groups. Postoperative hemoglobin was higher in the leuprolide group (P=0.003), but blood transfusion requirement was not different between the groups (P=1.0). Other outcomes and side effects of the drugs were similar. CONCLUSIONS: Goserelin and leuprolide administered before hysterectomy for uterine fibroids have similar perioperative outcomes.
BJU Int. 2008 May;101(9):1096-100.
Fujii Y, Yonese J, Kawakami S, Yamamoto S, Okubo Y, Fukui I.
Department of Urology, Cancer Institute Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan.
Equivalent and sufficient effects of leuprolide acetate and goserelin acetate to suppress serum testosterone levels in patients with prostate cancer.
OBJECTIVE: To compare the effects of leuprolide acetate and goserelin acetate for suppressing serum testosterone levels in Japanese patients with prostate cancer, as several recent studies suggested that serum testosterone is not always suppressed below the upper limit of the castration range in patients using luteinizing hormone-releasing hormone (LH-RH) agonists, especially leuprolide acetate. PATIENTS AND METHODS: In all, 232 patients with prostate cancer, whose serum testosterone levels were measured before and during treatment using a 1- or 3-monthly formulation of leuprolide or goserelin, were enrolled in a retrospective study. The mean age of the patients was 69.8 years and the mean testosterone level before the LHRH treatment was 4.54 ng/mL. The patients had their testosterone levels assessed a mean (range) of 5.4 (1-35) times during the LHRH treatment. A castrate serum testosterone level was defined as
Expert Opin Pharmacother. 2007 Feb;8(2):257-64.
Roach M 3rd, Izaguirre A.
Department of Radiation Oncology, University of California San Francisco, UCSF Comprehensive Cancer Center, San Francisco, California 94143-1708, USA.
Goserelin acetate in combination with radiotherapy for prostate cancer.
Improvements in longer-term survival rates have been demonstrated for locally advanced prostate cancer patients treated with adjuvant androgen deprivation therapy (ADT), and in subsets of men with clinically localized disease treated with ADT combined with external-beam radiotherapy (RT). In these studies, ADT was administered in the form of surgery (orchiectomy) or with a class of drugs called luteinizing hormone-releasing hormone agonists. Goserelin acetate is a member of this class, and 10 of 11 major Phase III trials demonstrating better outcomes with ADT and RT used goserelin acetate. The reduction in deaths from prostate cancer noted in the mid-1990s may largely be due to the early use of these agents in men with intermediate-to-high-risk disease.
Horm Res. 2007;68(4):157-63.
Isaac H, Patel L, Meyer S, Hall CM, Cusick C, Price DA, Clayton PE.
Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, UK.
Efficacy of a monthly compared to 3-monthly depot GnRH analogue (goserelin) in the treatment of children with central precocious puberty.
AIMS: To compare the efficacy of goserelin 10.8 mg (Zoladex LA-ZLA) administered 9-12 weekly with 3.6 mg (Zoladex-Z) given monthly in suppressing pubertal development, and effect on body mass index (BMI). METHODS: Children with central precocious puberty (CPP) treated with Z (n = 34) or ZLA (n = 28) were studied retrospectively. Pubertal scores and BMI SDS during 24 months' treatment were compared. RESULTS: To attain adequate pubertal suppression, more patients on ZLA than Z required increase in injection frequency (p = 0.02) and this was so for 7/8 patients with a structural aetiology for CPP on ZLA and 2/8 on Z. A greater proportion of patients on ZLA had BMI >+2 SDS before (p = 0.05), and at 18 and 24 months (p = 0.02 and 0.04). BMI SDS transiently increased during the first 6 months on ZLA (p = 0.04). CONCLUSION: Both Z and ZLA were effective in suppressing puberty. To achieve adequate suppression, increased injection frequency was more likely with ZLA than Z, and particularly in patients with structural defects. Children with CPP had an elevated BMI at the onset of therapy and ZLA had a transient positive influence on BMI.
Lancet Oncol. 2008 Aug 19.
Gnant M, Mlineritsch B, Luschin-Ebengreuth G, Kainberger F, Kässmann H, Piswanger-Sölkner JC, Seifert M, Ploner F, Menzel C, Dubsky P, Fitzal F, Bjelic-Radisic V, Steger G, Greil R, Marth C, Kubista E, Samonigg H, Wohlmuth P, Mittlböck
Department of Surgery, Medical University of Vienna, General Hospital Vienna, Vienna, Austria.
Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone-mineral density substudy.
BACKGROUND: The Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) bone substudy assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density (BMD) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid. The aim of this substudy is to gain insight into bone health in this setting. METHODS: ABCSG-12 is a randomised, open-label, phase III, 4-arm trial comparing tamoxifen (20 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days) versus anastrozole (1 mg/day orally) and goserelin (3.6 mg subcutaneously every 28 days), both with or without zoledronic acid (4 mg intravenously every 6 months) for 3 years in premenopausal women with endocrine-responsive breast cancer. This prospective bone subprotocol measured BMD at 0, 6, 12, 36, and 60 months. The primary endpoint of the bone substudy (secondary endpoint in the main trial) was change in BMD at 12 months, assessed by dual-energy X-ray absorptiometry in assessable patients. Analyses were intention to treat. Statistical significance was assessed by t tests. The ABCSG-12 trial is registered on the ClinicalTrials.gov website, number NCT00295646. FINDINGS: 404 patients were prospectively included in the bone substudy and randomly assigned to endocrine therapy alone (goserelin and anastrozole or goserelin and tamoxifen; n=199) or endocrine therapy concurrent with zoledronic acid (goserelin, anastrozole, and zoledronic acid or goserelin, tamoxifen, and zoledronic acid; n=205). After 3 years of treatment, endocrine therapy alone caused significant loss of BMD at the lumbar spine (-11.3%, mean difference -0.119 g/cm(2) [95% CI -0.146 to -0.091], p<0.0001) and trochanter (-7.3%, mean difference -0.053 g/cm(2) [-0.076 to -0.030], p<0.0001). In patients who did not receive zoledronic acid, anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine (-13.6%, mean difference -0.141 g/cm(2) [-0.179 to -0.102] vs -9.0%, mean difference -0.095 g/cm(2) [-0.134 to -0.057], p<0.0001 for both). 2 years after the completion of treatment (median follow-up 60 months [range 15.5-96.6]), patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline (lumbar spine -6.3%, mean difference -0.067 g/cm(2) [-0.106 to -0.027], p=0.001; trochanter -4.1%, mean difference -0.03 g/cm(2) [-0.062 to 0.001], p=0.058). Patients who received zoledronic acid had stable BMD at 36 months (lumbar spine +0.4%, mean difference 0.004 g/cm(2) [-0.024 to 0.032]; trochanter +0.8%, mean difference 0.006 g/cm(2) [-0.018 to 0.028]) and increased BMD at 60 months at both sites (lumbar spine +4.0%, mean difference 0.039 g/cm(2) [0.005-0.075], p=0.02; trochanter +3.9%, mean difference 0.028 g/cm(2) [0.003-0.058], p=0.07) compared with baseline. INTERPRETATION: Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss. Although there was partial recovery 2 years after completing treatment, patients receiving endocrine therapy alone did not recover their baseline BMD levels. Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years.
Zoladex description...
|
|
Drug category:Anti-cancer drugs
 Zoladex scientific update
|
|
My Basket