leuprolide and abarelix

Gonadotropin-releasing hormone agonists and antagonists provide androgen-deprivation therapy for prostate cancer. Unlike agonists, gonadotropin-releasing hormone antagonists have a direct mode of action to block pituitary gonadotropin-releasing hormone receptors. There are two licensed gonadotropin-releasing hormone antagonists, degarelix and abarelix. Of these, degarelix is the more extensively studied and has been documented to be more effective than the well-established, first-line agonist, leuprolide, in terms of substantially faster onset of castration, faster suppression of prostate-specific antigen, no risk for testosterone surge or clinical flare, and improved prostate-specific antigen progression-free survival, suggesting a delay in castration resistance. Other than minor injection-site reactions, degarelix is generally well tolerated, without systemic allergic reactions and with most adverse events consistent with androgen suppression or the underlying condition. In conclusion, degarelix provides a rational, first-line androgen-deprivation therapy suitable for the treatment of prostate cancer, with faster onset of castration than with agonists, and no testosterone surge. Furthermore, data suggest that degarelix improves disease control compared with leuprolide, and might delay the onset of castration-resistant disease. In view of these clinical benefits and the lack of need for concomitant anti-androgen treatment, gonadotropin-releasing hormone antagonists might replace gonadotropin-releasing hormone agonists as first-line androgen-deprivation therapy in the future.

Topics: Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Oligopeptides; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Prostate cancer is the most common nonskin cancer in the United States, with more than 2 million men currently living with the disease (Prostate Cancer Foundation, 2005). Hormone ablation therapy has resulted in much improved outcomes for thousands of men with this disease; however, there are often side effects that impact patients' quality of life. An overview of the use of hormone ablation therapy and the critical role nurses play for patients undergoing this treatment is provided.

Topics: 5-alpha Reductase Inhibitors; Androgen Antagonists; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Drug Monitoring; Finasteride; Flutamide; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Mass Screening; Neoplasm Staging; Nurse's Role; Nursing Assessment; Oligopeptides; Patient Education as Topic; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Quality of Life; Treatment Outcome

Cancer is a complex group of diseases. Many of the current treatment modalities available provide limited effectiveness and significant side effects. This circumstance creates a challenge for health care providers. There is great need for the development of innovative therapies that increase efficacy and decrease morbidity. In general, chemotherapeutic agents are unable to distinguish cancer cells from normal cells. As a result of therapy, patients may develop significant myelosuppression. Patients who are undergoing chemotherapy need to be observed for signs of hematologic and nonhematologic toxicities. Patients should be advised that periodic blood tests are indicated to monitor for anemia, neutropenia, and thrombocytopenia. If myelosuppression develops, measures to prevent complications such as bleeding and infection are indicated. Strategies to combat fatigue should also be discussed. Understanding of the biology of cancer has increased significantly in recent years. As knowledge of the science grows, new therapies are developed and clinical trials are initiated to investigate feasibility and efficacy of agents. Many of these trials involve agents that target specific biologic processes of cancer. While the complexities of cancer treatment are prolonging the life expectancy of patients who have the disease, patients are presenting with increasing numbers and types of morbidities. Nurses need to be aware of the rationale for treatment, mechanism of action of the agents administered, and expected toxicities of therapies. With this knowledge, symptoms can be identified earlier, life-threatening sequela can possibly be averted, and patients and families can be educated about what to expect and how to make knowledgeable decisions about treatment options. Enhancing patients' knowledge base may also increase their adherence to challenging therapies.

Topics: Adjuvants, Immunologic; Alemtuzumab; Aminoglycosides; Anastrozole; Androstadienes; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Benzamides; Bile; Boronic Acids; Bortezomib; Capecitabine; Cetuximab; Decanoic Acids; Deoxycytidine; Docetaxel; Drug Approval; Estradiol; Fluorouracil; Fulvestrant; Gefitinib; Gemtuzumab; Humans; Imatinib Mesylate; Letrozole; Leuprolide; Nitriles; Oligopeptides; Organoplatinum Compounds; Oxaliplatin; Oxides; Piperazines; Polyesters; Pyrazines; Pyrimidines; Quinazolines; Taxoids; Thionucleotides; Tissue Extracts; Triazoles; United States; United States Food and Drug Administration; Vidarabine Phosphate

In the 60 years since Huggins first demonstrated the hormone dependency of prostate cancer, the introduction of various means of hormonal manipulation has resulted in modest achievements. Orchiectomy reduced testosterone but was irreversible and associated with reduced quality of life. Diethylstilbestrol (DES) represented the first alternative to surgical castration. However, cardiovascular adverse events severely limited its use. The luteinizing hormone-releasing hormone (LHRH) agonists offered true medical castration but suffered from problems of testosterone surge and tumor flare. The introduction of antiandrogens in combination with LHRH agonists appears on meta-analysis not to have improved survival and has implications for the cost and convenience of therapy, as well as added toxicity. Gonadotropin-releasing hormone (GnRH) antagonists offer for the first time a truly rapid medical means of reducing testosterone and also suppress follicle-stimulating hormone (FSH). However, the clinical benefit of this new class of drugs remains to be evaluated.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Diethylstilbestrol; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Oligopeptides; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Study Type - Therapy (prospective cohort). Level of Evidence 2a. What's known on the subject? and What does the study add? The sequential administration of a GnRH antagonist followed by an LHRH agonist in the management of prostate cancer patients has not been studied, but such a program would provide a more physiologic method of achieving testosterone suppression and avoid the obligatory testosterone surge and need for concomitant antiandrogens that accompany LHRH agonist therapy. The current study which uses abarelix initiation therapy for 12 weeks followed by either leuprolide or goserelin demonstrates the ability to more rapidly achieve testosterone suppression, avoid the obligatory LHRH induced testosterone surge, avoid the necessity of antiandrogens, all of which were accomplished safely, without inducing either additional or novel safety issues.. • To demonstrate the safety and endocrinological and biochemical efficacy of initiating treatment with the gonadotropin-releasing hormone (GnRH) antagonist, abarelix, followed by administration of an luteinizing hormone-releasing hormone (LHRH) agonist in patients with advanced and metastatic prostate cancer.. • A multicentre, open-label design study was conducted at 22 centres in the US involving patients with: localized, locally advanced or metastatic disease; with a rising prostate-specific antigen (PSA) after definitive local treatment; patients undergoing neoadjuvant hormonal therapy before local therapy (radical prostatectomy, radiation therapy or cryosurgery); and patients in whom intermittent therapy was the planned treatment. • All patients received abarelix for 12 weeks followed by an LHRH agonist (either leuprolide or goserelin) for 8 weeks • The primary efficacy endpoint was achievement and maintenance of castration defined as testosterone <50 ng/dL from day 29 through to day 141 and whether abarelix initiation therapy could eliminate the testosterone surge after two consecutive doses of LHRH agonist therapy. • PSA, LH and follicle-stimulating hormone (FSH) levels were measured and adverse events were monitored.. • A total of 176 patients were enrolled into the present study, the majority of whom had localized prostate cancer (82%) and a PSA level <10 ng/mL (62%). • At the end of the abarelix treatment period (day 85), 93.8% of patients achieved castrate levels; during the first week of switch over to the LHRH agonist therapy (days 85-92) the rate was 86.5% and during the week after the second LHRH agonist injection (days 114-12) it was 93.3%. • A small, transient increase in testosterone occurred during the first injection of the LHRH agonist; mean (standard deviation [sd]) values increased from 17 (17.8) ng/dL at day 85 to 37.3 (51.07) ng/dL at day 86. • Mean (sd) PSA levels decreased from 20.5 (56.6) ng/mL at baseline to 3.7 (23.5) ng/mL on day 85 and remained stable throughout the LHRH agonist treatment phase. • Treatment-related adverse events occurred in 84% of patients overall; a similar incidence was reported during the two treatment phases.. • Abarelix initiation therapy results in the desired effect of achieving rapid testosterone suppression; testosterone surges after subsequent LHRH agonist therapy are greatly abrogated or completely eliminated. • This treatment paradigm (abarelix initiation followed by agonist maintenance) obviates the need for an antiandrogen. • Abarelix was well tolerated and no clinically meaningful or novel adverse events were observed during abarelix treatment or in the transition to LHRH agonist maintenance therapy.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Goserelin; Humans; Leuprolide; Male; Middle Aged; Oligopeptides; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; United States

We compared the endocrinological and biochemical efficacy of abarelix depot, a gonadotropin-releasing hormone antagonist, with that of a widely used combination of luteinizing hormone releasing hormone agonist and a nonsteroidal antiandrogen.. A total of 255 patients were randomized to receive open label 100 mg. abarelix depot or 7.5 mg. leuprolide acetate intramuscularly injection on days 1, 29, 57, 85, 113 and 141 for 24 weeks. Patients in the abarelix group received an additional injection on day 15 and those in the leuprolide acetate group received 50 mg. bicalutamide daily. Patients could continue treatment with study drug for an additional 28 weeks. The efficacy end points were the comparative rates of avoidance of testosterone surge (greater than 10% increase) within 7 days of the first injection and the rapidity of achieving reduction of serum testosterone to castrate levels (50 ng./dl. or less) on day 8. Patients were monitored for adverse events and laboratory abnormalities.. Abarelix was more effective in avoidance of testosterone surge (p <0.001) and the rapidity of reduction of testosterone to castrate levels on day 8 (p <0.001) than combination therapy. No significant difference was seen between the groups in the initial rate of decline of serum prostate specific antigen or the ability to achieve and maintain castrate levels of testosterone. No unusual or unexpected adverse events were reported.. Abarelix as monotherapy achieves medical castration significantly more rapidly than combination therapy and avoids the testosterone surge characteristic of agonist therapy. Both treatments were equally effective in reducing serum prostate specific antigen, and achieving and maintaining castrate levels of testosterone.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Humans; Leuprolide; Male; Middle Aged; Nitriles; Oligopeptides; Prostatic Neoplasms; Tosyl Compounds

We contrasted the endocrinological and biochemical efficacies of abarelix depot, a pure gonadotropin-releasing hormone antagonist, with a prospective concurrent control cohort receiving luteinizing hormone releasing hormone (LH-RH) agonists with or without antiandrogen for treatment of patients with prostate cancer receiving initial hormonal therapy.. In this phase 2 open label study 242 patients with prostate cancer requiring initial hormonal treatment received abarelix depot (209) or LH-RH agonists (33) with or without antiandrogen. A total of 100 mg. abarelix depot was delivered intramuscularly every 28 days with an additional injection on day 15. LH-RH agonists with or without antiandrogen were administered according to the depot formulation used. Endocrine efficacy was measured by the absence of testosterone surge and rapidity of castration onset. The rate of prostate specific antigen decrease was assessed.. No patient treated with abarelix depot had testosterone surge during week 1 compared with 82% of those treated with LH-RH agonists. The concomitant administration of antiandrogen had no effect. During the first week of drug administration, in 75% of patients treated with abarelix depot and in 0% of those treated with LH-RH agonist medical castration was achieved. Prostate specific antigen decrease was faster, with no flare or surge in patients treated with abarelix depot. Abarelix depot was well tolerated.. Abarelix depot represents a new class of hormonal therapy, gonadotropin releasing hormone antagonists, that has rapid medical castration and avoids the testosterone surge characteristic of LH-RH agonists.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Dihydrotestosterone; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Intramuscular; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Oligopeptides; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testis; Testosterone

To evaluate the levels of testosterone and other hormones in men with prostate cancer treated with abarelix versus leuprolide acetate.. Patients (n = 269) were randomized to receive open-label abarelix 100 mg or leuprolide acetate 7.5 mg by intramuscular injection. The results of the first 84 days of the study are reported. The primary efficacy endpoints included avoidance of testosterone surge, castration on day 8, and achievement and maintenance of castration from days 29 through 85. The secondary endpoints included castration on days 2, 4, and 15; a reduction in prostate-specific antigen level; and measurements of other hormones. Patients were monitored for clinical adverse events and laboratory abnormalities.. No men in the abarelix group and 82% of men in the leuprolide acetate group experienced a testosterone surge (P <0.001). Abarelix caused rapid medical castration: 24% of men 1 day after treatment and 78% after 7 days compared with 0% of men treated with leuprolide acetate on either day. A comparable percentage of men achieved and maintained castration between days 29 and 85 in each group. Prostate-specific antigen had a statistically significant decrease for the first month in patients treated with abarelix. Dihydrotestosterone, luteinizing hormone, prostate-specific antigen, and follicle-stimulating hormone showed similar rapid reductions without an initial increase. The overall occurrence of adverse events was similar across the treatment groups, and most were sequelae of comorbid disorders.. Treatment with abarelix produced a higher percentage of patients who avoided a testosterone surge and had a more rapid time to testosterone suppression with a higher rate of medical castration 1 day after treatment and greater reductions in testosterone, luteinizing hormone, follicle-stimulating hormone, and dihydrotestosterone during the first 2 weeks of treatment compared with leuprolide acetate. The achievement and maintenance of castration was comparable between the two groups.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers; Castration; Follicle Stimulating Hormone; Humans; Injections, Intramuscular; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Oligopeptides; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Time Factors

Although prostate cancer specific mortality is decreasing, there is little effect on overall mortality in this population, suggesting the possibility of an increased risk of death from nonprostate cancer related causes. Androgen deprivation therapy could adversely affect cardiovascular health. We investigated changes in lipid and glucose during androgen deprivation therapy.. We performed an exploratory analysis of pooled data from 3 prospective clinical trials aimed at achieving medical castration by comparing the gonadotropin releasing hormone antagonist abarelix, the gonadotropin releasing hormone agonist leuprolide acetate and leuprolide acetate plus the antiandrogen bicalutamide. Most patients were treated in the neoadjuvant setting or because of biochemical recurrence. Fasting serum lipid, glucose and hemoglobin A1C were determined in 1,102 men at baseline, and on treatment days 85 and 169. In the current study men were categorized into 3 treatment groups according to the type of androgen deprivation therapy, that is leuprolide acetate, leuprolide acetate plus bicalutamide or abarelix, and statin therapy.. Significant increases in total cholesterol, triglyceride and high density lipoprotein-cholesterol were observed in patients on leuprolide acetate or abarelix but not in patients on leuprolide acetate plus bicalutamide. Consistent changes in low density lipoprotein-cholesterol were not detected. Increased total cholesterol was usually due to an increase in high density lipoprotein-cholesterol. Hemoglobin A1C increased from baseline to day 85 only and there were no significant changes in fasting glucose measurements. The type of androgen deprivation therapy did not affect these parameters.. Short-term androgen deprivation therapy affects serum lipid and hemoglobin A1C independent of statin therapy.

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Blood Glucose; Cholesterol; Fasting; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Nitriles; Oligopeptides; Prostatic Neoplasms; Tosyl Compounds

Luteinizing hormone-releasing hormone (LHRH) antagonists work by directly inhibiting LHRH without any initial stimulation of the LHRH receptor. The physiologic response is a direct and rapid decrease in luteinizing hormone, follicle-stimulating hormone, and testosterone without any flare. Although there has been extensive basic-science work on these medications, practical shortcomings have limited clinical studies in prostate cancer. Many of these compounds induce significant histamine-mediated side effects, and until recently, no depot form existed. In 2 recent phase-3 studies comparing abarelix depot with leuprolide and with leuprolide plus bicalutamide, abarelix lowered serum testosterone more quickly. None of the 89 patients on leuprolide alone were castrate on day 8 as opposed to 72% of the 180 patients randomized to abarelix (P <0.001). Similarly, none of the combination group were castrate by day 8, whereas 68% of the abarelix patients were castrate (P <0.001). In addition, 82% of the patients treated with leuprolide and 86% of those given leuprolide/bicalutamide had testosterone surge, whereas none of the abarelix patients did (P <0.001 for both studies). Both phase 2 and phase 3 data show abarelix to be well tolerated. In conclusion, LHRH antagonists offer the physiologic response of orchiectomy without surgery. These medications are well tolerated and a depot form now exists. The expansion of indications for androgen deprivation, such as downsizing or intermittent therapy, could provide many opportunities for their use. Despite these encouraging advances, however, their routine use for advanced prostate cancer may depend on demonstration of a survival advantage in avoiding flare.

Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Disease-Free Survival; Gonadotropin-Releasing Hormone; Hormone Antagonists; Humans; Leuprolide; Male; Oligopeptides; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Testosterone; Therapeutics; Treatment Outcome