3-month Formulation Research Articles

Efficacy and Safety of Leuprolide Acetate 3-Month Depot 11.25 Milligrams or 30 Milligrams for the Treatment of Central Precocious Puberty

GnRH agonist (GnRHa) monthly injections are frequently used in the treatment of central precocious puberty (CPP). The 3-month leuprolide depot 11.25- and 30-mg formulations are newly approved treatment options. The aim of the study was to investigate the safety and efficacy of leuprolide acetate 3-month depot formulations for the treatment of CPP in children. This was a phase III, randomized, open-label, dose-ranging 6-month study. Twenty-two U.S. medical centers (including Puerto Rico) participated. Children diagnosed with CPP (n = 84), who were either treatment naive or previously treated with GnRHa, were recruited. Chronological age at onset of pubertal signs was less than 8 yr in girls and less than 9 yr in boys, and bone age was advanced over chronological age at least 1 yr. Leuprolide acetate depot (11.25 or 30 mg) was administered im every 3 months. Biochemical [peak-stimulated LH, estradiol (girls), and testosterone (boys)] and anthropometric (growth rate, bone age acceleration, pubertal progression) parameters and safety were assessed. Peak-stimulated LH was suppressed in the 11.25- and 30-mg dose groups in 78.4 and 95.2%, respectively, of children from months 2 through 6. There were nine treatment failures (peak-stimulated LH >4 IU/liter) in the 11.25-mg group and two in the 30-mg group. Basal sex steroid suppression, growth rates, pubertal progression, bone age advancement, and adverse events were similar with either dose. Treatment with leuprolide acetate 3-month depot formulations (11.25 and 30 mg) effectively suppressed the GnRH axis, was well tolerated, and may positively impact patient convenience and compliance.

Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer

Background:This open-label study evaluated the efficacy and safety of a new leuprolide acetate 45 mg 6-month depot formulation in 151 men with prostate cancer who received 2 intramuscular injections administered 24 weeks apart.Methods:The primary efficacy measurement was the proportion of patients achieving suppression of serum testosterone to ⩽50 ng dl−1 from week 4 through week 48. Adverse events (AEs) and hormonal and safety laboratory values were monitored.Results:The primary efficacy end point was achieved in 93.4% of subjects (95% confidence interval (89.2%, 97.6%)). There were nine escapes from testosterone suppression during the study, none of which were accompanied by a rise in PSA. By week 4, mean testosterone concentration was suppressed below castrate levels to 15.9 ng dl−1; suppression was maintained for the entire 24-week duration of each depot injection. No mean increase in testosterone was observed after the second injection. Mean PSA levels were maintained below 3 ng ml−1 from week 14 through the 48-week treatment period. The most frequent AE was flushing (58.3%). Injection site reactions were reported in 24.5% of patients.Conclusions:Leuprolide acetate 45 mg 6-month depot demonstrated rapid and sustained testosterone suppression through 12 months and was well tolerated. This 6-month leuprolide acetate depot will decrease the number of annual injections in the treatment of prostate cancer.

A 6-month depot formulation of leuprolide acetate is safe and effective in daily clinical practice: a non-interventional prospective study in 1273 patients

BackgroundTestosterone stimulates growth in many prostate tumours. The established GnRH analogue leuprolide acetate is incorporated in a novel biodegradable polymer matrix (Atrigel® delivery system), that can be administered to reduce testosterone levels in men with advanced hormone-dependent prostate cancer. This novel formulation is available as a 1-, 3- and most recently 6-month depot (Eligard® 45 mg). The latter was shown to lower and maintain safe and effective serum testosterone suppression in a clinical study.MethodsA non-interventional study to confirm the efficacy and safety of 6-monthly leuprolide acetate (Eligard® 45 mg) in routine urological practice was performed in Germany. Data were obtained from 1273 patients under the care of 634 urologists, and were analysed descriptively. Concentrations of PSA and serum testosterone were documented at the baseline visit and at 6 and 12 months following 6-monthly leuprolide acetate. The participating physicians were also asked to assess the efficacy, tolerabilty and handling of 6-monthly leuprolide acetate.ResultsSerum concentrations of PSA and testosterone were decreased substantially within 6 months of initial 6-monthly leuprolide acetate administration. At 12 months, median reductions of 96% (to 0.5 ng/ml) in PSA, and 90% (to 8.9 ng/dl) in serum testosterone, were observed. Further PSA and serum testosterone decreases were also observed in a subpopulation of patients who switched to 6-monthly leuprolide acetate from other GnRH analogues. Physicians rated 6-monthly leuprolide acetate as easy to use, and patients reported good tolerability. Adverse events occurred in 9% of patients; the majority were not serious. In particular, low rates of hot flushes were reported.ConclusionsThis non-interventional study showed that the reliable reduction of PSA and testosterone levels demonstrated in previous clinical studies of twice-yearly leuprolide acetate can also be achieved in routine clinical practice. This study also confirmed good tolerability of 6-monthly leuprolide acetate in routine clinical use and received positive appraisal from physicians.

A Randomized Trial of 1- and 3-Month Depot Leuprolide Doses in the Treatment of Central Precocious Puberty

To compare 1-month and 3-month depot formulations of leuprolide acetate (DL), a gonadotropin-releasing hormone analog, in the treatment of central precocious puberty (CPP). Subjects with CPP naïve to therapy were randomized to 7.5 mg of 1-month DL, 11.25 mg of 3-month DL, or 22.5 mg of 3-month DL. Stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and estradiol levels, growth velocity, and bone age progression were examined in a 2-year period. Forty-nine female and 5 male subjects with CPP were randomized. Mean stimulated LH and FSH levels during treatment were higher in the low-dose 11.25-mg 3-month DL group, and more LH levels >4 IU/L were observed, in comparison with the other two dose groups. Mean LH and FSH levels in the 22.5-mg 3-month group were not different from the monthly DL. No differences in estradiol levels, growth velocity, or bone age progression were observed in dosing groups. All DL doses resulted in prompt and effective suppression of puberty, but higher LH and FSH levels were seen with the 11.25-mg 3-month DL dose. Multi-monthly DL is effective in treating CPP, but higher dosing may be required in some circumstances.

Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort.

Two different 6-month GnRH agonist depot formulations approved for palliative treatment of advanced and metastatic prostate cancer in the United States – leuprolide acetate 45 mg and triptorelin pamoate 22.5 mg – provide patients with efficacy and safety comparable to those of existing 1-, 3-, and 4-month GnRH agonist depots. However, the 6-month formulations can increase patient convenience, comfort, and compliance by reducing the number of physician visits and injections required. At the conclusion of their pivotal trials, the 6-month formulations demonstrated efficacy rates in achieving chemical castration (serum testosterone ≤50 ng/dL) that ranged between 93% and 99%. As with existing GnRH agonist depot formulations, hot flashes represented the most common adverse event reported in trials of 6-month leuprolide acetate or triptorelin. As such, these products may prove useful not only for their labeled indication, but also as adjuncts to other treatments such as radical prostatectomy, radiotherapy, and chemotherapy. We recommend further research, including head-to-head trials between the 6-month GnRH depots, to refine our understanding of these products.

Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort

Six-month gonadotropin releasing hormone (GnRH) agonist depots provide efficacy, safety, convenience, and comfort E David Crawford, Jason M PhillipsUniversity of Colorado Health Sciences Center, Aurora, CO, USAAbstract: Two different 6-month GnRH agonist depot formulations approved for palliative treatment of advanced and metastatic prostate cancer in the United States – leuprolide acetate 45 mg and triptorelinpalmoate 22.5 mg – provide patients with efficacy and safety comparable to those of existing 1-, 3-, and 4-month GnRH agonist depots. However, the 6-month formulations can increase patient convenience, comfort, and compliance by reducing the number of physician visits and injections required. At the conclusion of their pivotal trials, the 6-month formulations demonstrated efficacy rates in achieving chemical castration (serum testosterone #50 ng/dL) that ranged between 93% and 99%. As with existing GnRH agonist depot formulations, hot flashes represented the most common adverse event reported in trials of 6-month leuprolide acetate or triptorelin. As such, these products may prove useful not only for their labeled indication, but also as adjuncts to other treatments such as radical prostatectomy, radiotherapy, and chemotherapy. We recommend further research, including head-to-head trials between the 6-month GnRH depots, to refine our understanding of these products.Keywords: prostate cancer, leuprorelin, leuprolide, triptorelin, 6-month depot, testosterone

Pharmacological treatment of sex offenders

Summary Sex offending is a major public health concern due to the potentially serious consequences for the victims (especially in case of rape or paedophilia). All care providers agree that imprisonment alone does not solve the question of repeat offences for these subjects and that a combined medical, psychological and social approach is needed for these offenders. A combination of psychotherapy (especially behavioral therapy) with pharmacological treatment is better than one or other therapy used alone. Two types of medication are used for these subjects; serotonergic antidepressants and antiandrogen treatments. Two antiandrogen treatments have obtained Health Agency approval in different European countries in this indication: cyproterone acetate and depot triptorelin (3-month formulation). Guidelines have been published in France by the National Health Authority and, at the international level, by the World Federation of Societies of Biological Psychiatry ( www.wfsbp.org ). In this paper, we will define the term paraphilia and report some epidemiological data, before summarizing the available literature about the efficacy of pharmacological treatment for paraphilias.

Efficacy of triptorelin in lowering serum testosterone (sT) in patients with advanced prostate cancer.

162 Background: Medical castration using gonadotropin-releasing hormone (GnRH) agonists is the mainstay of treatment for advanced prostate cancer. Achievement and maintenance of castrate serum testosterone (sT) levels <50 ng/dL (1.735 nmol/mL) has been the goal of therapy. However, patients are able to achieve and maintain sT levels <15 ng/dL after surgical castration (Oefelein M et al. J Urology 2000; 56: 1021-4). Some authors have suggested that 20 ng/dL should be the target threshold for medical castration(Perachino M et al. BJU Int 2010; 105: 648-51) but the clinical relevance of achieving such low sT levels (<20 ng/dL) remains unknown. Methods: The efficacy and safety of sustained-release triptorelin pamoate 22.5 mg 6-month formulation was recently evaluated in a 12-month (48-week), multicentre, open-label, phase III study in 120 patients with locally advanced or metastatic prostate cancer and/or increased prostate specific antigen (PSA) after failed local therapy. Initial results based on the standard castration level of 50 ng/dL were previously presented in comparison to triptorelin 1- and 3-month formulations (Lundström E et al. Clin Drug Investig 2009; 29: 757-65). We report the proportions of patients achieving sT levels of <20 ng/dL with the triptorelin pamoate 1-, 3- and 6-month formulations. Results: With the 6-month formulation, sT levels of <20 ng/dL were achieved in >90% of patients on Day 169 (6 months after first triptorelin injection) and on Day 337 (6 months after second injection; Table). Similar sT levels were achieved with triptorelin 1- and 3-month formulations in a phase III study over 9 months (Table). Conclusions: A high proportion of patients receiving the 6-month triptorelin formulation achieve sT levels <20 ng/dL. This compares favorably to the triptorelin 1- and 3-month formulations. [Table: see text] [Table: see text]

Cost-effectiveness analysis of LHRH agonists in the treatment of metastatic prostate cancer in Italy

Objectives Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with metastatic prostate cancer. We compared the cost-effectiveness of the five different 3-month formulations of LHRH agonists currently available for advanced prostate cancer in Italy, because these differ both in their capacity to suppress testosterone and in their acquisition costs. Methods A probabilistic, patient-level simulation model was developed to compare the cost-effectiveness, from the perspective of the Italian National Health Service (INHS), of leuprorelin 11.25 mg and 22.5 mg, triptorelin 11.25 mg, buserelin 9.9 mg, and goserelin 10.8 mg. The model incorporated testosterone-dependent progression-free and cancer-specific survival functions, LHRH agonist effectiveness data, and national costs and tariffs. Cox's proportional hazard models were used to compute total and progression-free survival functions based on clinical data from 129 patients with metastatic prostate cancer treated in an Italian center. Bayesian random effects models were employed to summarize evidence from published literature on testosterone suppression obtained with the available LHRH agonists. Results Estimated total survival was ≈5 years, with a maximum difference between treatment options of ≈2 months. There was a mean difference of almost €2,500 in lifetime total costs between the least costly option (leuprorelin 22.5 mg) and the most expensive (goserelin ). In the incremental cost-effectiveness analysis, leuprorelin 22.5 mg dominated all alternatives except buserelin, which had an incremental cost-effectiveness ratio versus leuprorelin 22.5 mg of ≈€12,000 per life-month gained. Conclusions Based on modelling with meta-analysis of comparative survival data, leuprorelin 22.5 mg was the most cost-effective treatment of the available depot formulation LHRH agonists.

Triptorelin embonate: a 6-month formulation for prostate cancer

Importance of the field: Luteinizing hormone releasing hormone (LH RH) agonists are the major agent for androgen deprivation therapy in advanced and metastatic prostate cancer. They also have a role in endometriosis, uterine fibroids and central precocious puberty.Areas covered in the review: Triptorelin embonate 22.5 mg is a new, sustained-release, 6-month formulation of an LH RH agonist. It possesses longer duration of action than the current standard 3-month preparation and appears to have similar efficacy and side effects.What the reader will gain: The use of LH RH agonists for androgen deprivation in prostate cancer has increased considerably in the last 20 years. Recent work has shown that some of this usage has constituted overtreatment and it is within these newer paradigms of therapy that the new 6-month preparation is situated.Take home message: The new 6-month LH RH preparation – triptorelin embonate – will be of help in several key areas of therapy for prostate cancer, notably as an adjunct to radiation therapy and chemotherapy. It possesses a similar effect, but with fewer side effects, than those that are now commonly available.

Triptorelin embonate (6-month formulation): a guide to its use in advanced prostate cancer

Triptorelin embonate (6-month formulation): a guide to its use in advanced prostate cancer

Triptorelin Embonate (6-Month Formulation)

A 6-month formulation of the gonadotropin-releasing hormone agonist triptorelin embonate (designed to deliver 22.5 mg of triptorelin over a 6-month period) has been developed for use in the treatment of advanced prostate cancer. Following intramuscular administration of the 6-month formulation of triptorelin embonate 22.5 mg to men with advanced prostate cancer (subset of 15 patients from the pivotal clinical trial), serum testosterone levels initially increased, followed by a rapid, sustained decrease. Castrate serum testosterone levels (i.e. < or =1.735 nmol/L) were achieved in a geometric mean time of 18.8 days. The 6-month formulation of triptorelin embonate achieved and maintained castrate serum testosterone levels in patients with advanced prostate cancer (n = 120), according to the results of the pivotal, noncomparative, multicentre trial (patients received intramuscular triptorelin embonate 22.5 mg on day 1 and at month 6 [week 24]). By day 29, 97.5% of patients had castrate serum testosterone levels. Castrate serum testosterone levels were maintained from months 2 to 12 in 93.0% of patients. Prior to the second injection at month 6, 98.3% of patients had castrate serum testosterone levels, and 98.3% of patients had castrate serum testosterone levels at study completion. The 6-month formulation of triptorelin embonate 22.5 mg was generally well tolerated in patients with advanced prostate cancer; adverse events were of mild severity in the majority of patients. Drug-related adverse events (e.g. hot flushes) were consistent with the pharmacological action of triptorelin. Injection-site reactions occurred in 6.7% of triptorelin embonate recipients.

LEUPRORELIN ACETATE DEPOT (ELIGARD) IN THE TREATMENT OF PROSTATE CANCER: WHAT DO PATIENTS WIN?

Eligard (leupropelin acetate, Atrigel delivery system) is a synthetic analogue of luteinizing-hormone-realizing hormone (LHRH), which causes a rapid reduction in the level of testosterone to the concentration comparable with that after surgical castration. Eligard demonstrated a considerable advantage over other LHRH analogues in the depth of androgenic suppression and in the frequency of transient increases in testosterone levels at the beginning and during therapy. Eligard is available as 1-, 3-, and 6-month depot formulations, which allows a flexible approach to be applied to individually making up a therapy regimen. Eligard is as effective as castration therapy techniques. Treatment with this drug shows the low frequency of side effects and is well tolerated by patients.

Triptorelin 6-Month Formulation in the Management of Patients with Locally Advanced and Metastatic Prostate Cancer

Triptorelin 6-month formulation was developed to offer greater convenience to both patients and physicians by reducing the injection frequency. The efficacy, pharmacokinetics and safety of a new 6-month formulation of triptorelin were investigated over 12 months (48 weeks). The primary objective was to evaluate the formulation in achieving castrate serum testosterone levels (< or = 1.735 nmol/L or < or = 50 ng/dL) on day 29 and in maintaining castration at months 2-12. Absence of luteinizing hormone (LH) stimulation and change in prostate-specific antigen (PSA) level were also assessed. An open-label, non-comparative, phase III study in 120 patients with advanced prostate cancer was conducted from July 2006 to August 2007 in private and public institutions in South Africa. Each patient received two consecutive intramuscular injections of triptorelin embonate (pamoate) 22.5 mg at an interval of 24 weeks. In all patients, testosterone (primary outcome measurement) was measured at baseline and then every 4 weeks; LH was measured before and 2 hours after the two injections. PSA was measured on day 1 and at weeks 12, 24, 36 and 48. Adverse events were recorded at each visit. In the intent-to-treat population, 97.5% (95% CI 92.9, 99.5) of patients achieved castrate serum testosterone levels by day 29, and 93.0% (95% CI 86.8, 97.0) maintained castration at months 2-12. After the second injection, 98.3% of patients showed absence of LH stimulation. The most frequent drug-related adverse events were hot flushes (71.7% of patients). No patient withdrew from the study as a result of an adverse event. The triptorelin 6-month formulation was well tolerated and was able to achieve and maintain castration for the treatment of locally advanced and metastatic prostate cancer. By reducing the frequency of required injections, this new formulation offers a more convenient treatment regimen. (Clinical Trial Registration,NCT00751790 at www.clinicaltrials.gov).

Triptorelin improves intestinal symptoms among patients with colorectal endometriosis

⁎ Corresponding author. Department of Obstetrics and Gynecology, San Martino Hospital, Largo R. Benzi 1, 16132 Genoa, Italy. Tel./fax: +39 10 511 525. E-mail address: dr@simoneferrero.com (S. Ferrero). Little attention has been given to the role of hormonal therapies in treating symptoms caused by bowel endometriosis [1]. The aim of the present open-label prospective study was to evaluate the effects of GnRH analogues (GnRH-a) on pain and intestinal symptoms among patients with colorectal endometriosis. Multidetector computerized tomographyenteroclysis (MDCT-e)was used to determine the presence and severity of colorectal endometriosis [2]. Inclusion criteria for the study were reproductive age, pain and gastrointestinal symptoms suggestive of bowel endometriosis (persisting for at least 12 months), and colorectal nodules infiltrating at least the muscularis propria of the bowel. Exclusion criteria were stenosis of the bowel lumen greater than 60% and presence of endometriotic nodules located on the cecum or the ileum. Study participants received depot intramuscular injections of the 3-month formulation of triptorelin (11.25 mg; Decapeptyl, Ipsen Pharma, Milan, Italy) and oral tibolone (2.5 mg daily; Livial, Organon, Rome, Italy) for 12 months. Patients were allowed to take nonsteroidal anti-inflammatory drugs for the treatment of pain (550 mg naproxen sodium tablet; Synflex Forte 550, Recordati Industria Chimica e Farmaceutica, Milan, Italy) and lactulose (dose of 10 g per 15 mL; Laevolac, Roche, Milan, Italy) for the treatment of constipation. Presence and intensity of symptoms were evaluated before starting the treatment andafter 6 and12 months of treatment. At completion, the overall degree of patient satisfactionwith the treatmentwas determined by responses given to the following question: “Taking into consideration the variations in pain symptoms, overall well-being, and quality of life, as well as any adverse effects experienced, howwould you define the level of satisfaction with your treatment?” [3]. Patients were also asked whether their intestinal symptoms changed during treatment. The local Institutional Review Board approved the study protocol. Patients were informed that surgery is the standard treatment for symptomatic bowel endometriosis [1,4] and the potential benefits and complications of surgery were explained in detail. All study subjects wished to avoid or postpone surgery and requested amedical therapy. Patients were also told that hormonal therapies are not expected to be definitely curative of endometriosis [5]. Study participants provided written informed consent. Variations in grading of symptoms between baseline and follow-up were compared using the paired t test and the signed rank test according to data distribution. Eighteen women were included in the study, with a mean age of 36.1±4.7 years. The larger endometriotic bowel nodule was located on the sigmoid in9women,on the rectosigmoid junction in5women, and on the rectum in 4 women. The mean estimated size of the larger colorectal nodulewas2.2±0.6 cmand themeanestimatedstenosisof the bowel lumenwas42.0%±9.7%.At the 12-monthassessment of the effects of therapy on the symptoms, 13 (72.2%) women were very satisfied or satisfied, 2 (11.1%) were uncertain, and 3 (16.7%) were dissatisfied. Intestinal symptomswere unchanged during treatment in 7 (38.9%) women, while 11 patients (61.1%) reported some improvements in intestinal function. Table 1 shows that patients with symptoms mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) reported improvements in intestinal symptoms significantly more frequently than those with symptoms mimicking constipationpredominant irritable bowel syndrome (IBS-C; 100.0% vs 14.3,P=0.003). The severity of dysmenorrhea, nonmenstrual pelvic pain, deep dyspareunia, anddyscheziawasmeasuredusing a 10-cmvisual analogue scale (VAS). The treatment significantly decreased the intensity of pain symptoms (Table 2). The severity of the intestinal symptoms was measured using a symptom analogue scale questionnaire (1 indicated the absence of the symptom; 10 indicated the highest severity of the symptom). IBS-D, intestinal cramping, abdominal bloating, and passage of mucus improved during treatment; no significant change was observed in IBS-C and feeling of incomplete evacuation (Table 2). The number of naproxen sodium tablets used by patients decreased during treatment; the number of lactulose doses used by patients did not change during treatment (Table 2). Fifteen women (83.3%) reported at least 1 adverse effect (hot flushes, n=6; vaginal bleeding, n=6; sweating episodes, n=3; vaginal dryness and superficial dyspareunia, n=2; nervousness and irritability, n=2; loss of libido, n=2; weight gain, n=2; sleeplessness, n=1; difficulty in concentrating, n=1; fatigue, n=1). At the completion of the study, 7 patients (38.9%) continued the treatment with triptorelin and tibolone; 50.0% of the patients with IBS-D continued the treatment with triptorelin versus 14.3% of the patients with IBS-C (P=0.282).

Six-month depot formulation of leuprorelin acetate in the treatment of prostate cancer.

Hormonal deprivation therapy is well established for the treatment of locally advanced and metastatic prostate cancer, as well as the adjuvant treatment of some patients with localized disease. Long-acting gonadotropin releasing hormone (GnRH) agonists have become a mainstay of androgen deprivation therapy, due to their efficacy, tolerability, and convenience of use. One-month, 3-month, and 4-month depot leuprorelin formulations are well established and widely used to this end. Recently, a 6-month depot leuprorelin has been approved for use in advanced and metastatic prostate cancer patients. With similar efficacy and side effect profiles to earlier formulations, 6-month depot leuprorelin is a convenient treatment option for these patients. This review will highlight the role of GnRH agonists in the treatment of prostate cancer with a focus on the clinical efficacy, pharmacology, and patient-focused outcomes of the newer 6-month 45 mg depot leuprorelin formulation in comparison to available shorter-acting products.

Safety and clinical efficacy of a new 6-month depot formulation of leuprorelin acetate in patients with prostate cancer in Europe

This multicentre European study compared the safety and tolerability of the existing 11.25 mg 3-month depot of leuprorelin acetate with a new 30 mg 6-month depot in men with newly diagnosed prostate cancer or prostate-specific antigen relapse after radiotherapy or prostatectomy. The primary end points were safety and tolerability and secondary end points were clinical response based on European Organization for Research and Treatment of Cancer (EORTC) criteria and response rate by time point for testosterone suppression (castrate level <or=50 ng per 100 ml). Results showed that the incidence of adverse events was similar with the different depot formulations, with hot flushes being the most common. The assessment of EORTC response criteria showed comparable results in each arm with a tumour progression rate of <10% at the final examination at month 12. Testosterone suppression was comparable with the different formulations. In conclusion, the 6-month depot formulation of leuprorelin acetate containing 30 mg is well tolerated and safe and has been shown to be as effective as the widely used 3-month depot containing 11.25 mg leuprorelin acetate in the treatment of prostate cancer.

The relationship between LHRH-agonist depot formulations and frequency of follow-up with health care providers in patients with prostate cancer

16002 Background: Several formulations of Luteinizing Hormone-Releasing Hormone Agonists (LHRH-A) of varying duration are available for treatment of prostate cancer (PCa). Previous reports suggest that utilization of longer acting LHRH-A may reduce the number of healthcare visits, thereby reducing the costs of managing PCa patients. In this study we investigated the frequency of patient follow-up with respect to use of 1, 3 and 4 month depot formulations in a cohort of patients with PCa from a large healthcare system in the United States. Methods: Data from PCa patients identified in the Henry Ford Health System (HFHS) as International Classification of Diseases for Oncology (ICD-O) code C61.9 in the tumor registry were extracted. The following patients were included: full staging information at index and the same dosage of LHRH-A during the duration of the follow-up. Patients with prior primary tumor types were excluded. Results: 653 patients receiving the same depot of LHRH-A through the duration of agonist treatment were identified (44.1 % Caucasians, mean age 72±9.2, mean Gleason score 7.2, median PSA 10.5). There was no significant difference with depot switchers excluded from the analysis. Patients receiving 1, 3 and 4-month depot formulations had 25, 29 and 41 days between any PCa related visits. Patients on the 1-month depot had 51 days between visits to urologists, while patients on 3 and 4 month depots had 46 and 60 days between urologist visits, respectively. For patients receiving 1-month depot, there was no significant difference between the actual time between PCa related follow-up visits and expected time between follow-up visits (mean difference -5 days; p=0.1923). However, patients receiving 3-month (mean difference -61 days; p<0.0001) and 4-month (mean difference -79 days; p<0.0001) depot formulations had significantly less time than expected between PCa related follow-up visits. Conclusions: Although it was expected that the depot formulation would have a significant impact on the interval between PCa related visits, the data did not support this. The results of this study suggest that patients’ frequency of follow- up with health care providers is not influenced by LHRH-A depot formulations. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ferring Ferring Ferring Ferring

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 ≈ 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 ⩾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.

Assessing the attitudes to prostate cancer treatment among European male patients

To understand the attitudes of patients with prostate cancer toward the disease in general and to the use of hormone therapy as treatment; to assess unmet needs in the management of prostate cancer; and to gauge patient receptivity to a potential 6-month formulation of a luteinizing hormone-releasing hormone (LHRH) agonist. Face-to-face interviews, lasting 50 min on average, were conducted during January and February 2007 with 200 European men who had been diagnosed with prostate cancer. Most patients were very satisfied with their physician, particularly with specialists, with 94% of men being satisfied with their expertise and 67% fully trusting the recommended treatment. Therapeutic efficacy was considered the most crucial aspect of treatment, although maintaining their lifestyle during treatment was also considered important (83% of patients). In all, 67% of patients believed that consideration should be given to lifestyle needs when selecting treatment; however, over half (55%) had never raised lifestyle issues with their physicians. Most patients would prefer fewer injections, with 68% preferring 6-monthly injections over 3- or 1-monthly depots. Perceived advantages of 6-monthly injections include less discomfort/pain, more quality of life, fewer reminders of the disease and more ability to undertake activities without restriction. Patients with prostate cancer are generally very satisfied with their physicians and the information they receive, yet find it difficult to communicate their lifestyle needs. Most patients would prefer 6-monthly LHRH agonist therapy due to the many advantages associated with fewer injections, including its efficacy in reducing testosterone levels. Improving patients' willingness to raise lifestyle issues with their physicians, providing more effective patient-physician communication and less frequent injections might assist in achieving both optimal control of testosterone and optimal management of prostate cancer.