Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new lupron research articles will be listed here shortly after becoming available to us.
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Medical research on lupron
Phase II trial of docetaxel with rapid androgen cycling for progressive noncastrate prostate cancer.
J Clin Oncol. 2008 Jun 20; 26(18): 2959-65
Rathkopf D, Carducci MA, Morris MJ, Slovin SF, Eisenberger MA, Pili R, Denmeade SR, Kelsen M, Curley T, Halter M, Collins C, Fleisher M, Heller G, Baker SD, Scher HI
PURPOSE: We evaluated rapid androgen cycling in combination with docetaxel for men with progressive noncastrate prostate cancers. PATIENTS AND METHODS: Noncastrate patients with 150 ng/dL) and an undetectable prostate-specific antigen (PSA;
Fertil Steril. 2008 Jun 12;
Kahraman K, Berker B, Atabekoglu CS, Sonmezer M, Cetinkaya E, Aytac R, Satiroglu H
OBJECTIVE: To compare the efficacy of microdose GnRH agonist (GnRH-a) flare-up and multiple dose GnRH antagonist protocols in patients who have a poor response to a long luteal GnRH-a protocol. DESIGN: Prospective, randomized, clinical study. SETTING: University hospital. PATIENT(S): Forty-two poor responder patients undergoing intracytoplasmic sperm injection (ICSI)-embryo transfer cycle. INTERVENTION(S): Twenty-one patients received microdose leuprolide acetate (LA) (50 mug twice daily) starting on the second day of withdrawal bleeding. The other 21 patients received 0.25 mg of cetrorelix daily when the leading follicle reached 14 mm in diameter. MAIN OUTCOME MEASURE(S): Serum E(2) levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate and pregnancy rate (PR). RESULT(S): The mean serum E(2) concentration on the day of hCG administration was significantly higher in the microdose GnRH-a group than in the GnRH antagonist group (1,904 vs. 1,362 pg/mL). The clinical PRs per started cycle of microdose GnRH-a and GnRH antagonist groups were 14.2% and 9.5%, respectively. There were no statistically significant differences in the other ovulation induction characteristics, fertilization and implantation rates. CONCLUSION(S): Microdose GnRH-a flare-up protocol and multiple dose GnRH antagonist protocol seem to have similar efficacy in improving treatment outcomes of poor responder patients.
J Clin Endocrinol Metab. 2008 Jun 10;
Recabarren SE, Sir-Petermann T, Rios R, Maliqueo M, Echiburú B, Smith R, Rojas-García P, Recabarren M, Rey RA
Context: An important proportion of male members of PCOS families exhibit insulin resistance and related metabolic defects. However, the reproductive phenotypes in first- degree male relatives of PCOS women have been less described. Objective: To evaluate the pituitary-testicular function in sons of women with PCOS during different stages of life: early infancy, childhood and adulthood. Design: Eighty sons of women with PCOS (PCOSS) and 56 sons of control women without hyperandrogenism (CS), matched for age, were studied. In all subjects, the pituitary-gonadal axis was evaluated by a GnRH agonist test (leuprolide acetate, 10 ug/Kg s.c.). Serum anti-Müllerian hormone (AMH) and inhibin B were used as Sertoli cell markers. Serum concentrations of gonadotropins, steroid hormones, sex hormone binding globulin (SHBG) were also determined. In a semen analysis was performed. Results: Basal concentrations of gonadotropins, sex steroids and inhibin B were comparable between PCOSs and CS during early infancy, childhood and adulthood. Similar results in stimulated gonadotropin and sex steroid concentrations were observed. However, AMH serum concentrations were higher in PCOSs compared to CS during early infancy [925.0 (457.3 - 1401.7) pmol/l vs 685.6 (417.9 - 1313.2) pmol/l, p=0.039] and during childhood [616.3 (304.6 - 1136.9) pmol/l vs 416.5 (206.7 - 801.2) pmol/l, p=0.007). Sperm-count analysis was similar between both groups. Conclusions: AMH concentrations are increased in prepubertal sons of women with PCOS, suggesting that these boys may show an increased Sertoli cell number or function during infancy and childhood. However, this does not seem to have a major deleterious effect on sperm production.
Neuropeptides. 2008 Jun 2;
Umathe SN, Bhutada PS, Jain NS, Shukla NR, Mundhada YR, Dixit PV
Corticotrophin-releasing factor (CRF) is reported to inhibit the release of gonadotropin-releasing hormone (GnRH). In addition to the endocrine effects, GnRH is reported to influence the behavior via its neuronal interactions. We therefore, hypothesized that anxiety and depression produced by CRF could be also subsequent to the decrease in GnRH. To support such possibility, we investigated the influence of GnRH agonists on CRF or CRF antagonist induced changes in social interaction time in social interaction test, and immobility time in forced swim test in mice, as the indices for anxiety and depression, respectively. Results indicated that GnRH agonists [leuprolide (20-80ng/mouse, i.c.v.), or d-Trp-6-LHRH (40-160ng/mouse, i.c.v.)] dose dependently increased social interaction time and decreased immobility time indicating anxiolytic- and antidepressant-like effect, respectively. Such effects of GnRH agonists were even evident in castrated mice, which suggest that these effects were unrelated to their endocrine influence. Administration of CRF (0.1 and 0.3nmol/mouse, i.c.v.) produced just opposite effects as that of GnRH agonist on these parameters. Further, it was seen that pretreatment with leuprolide (10 or 20ng/mouse, i.c.v.) or d-Trp-6-LHRH (20 or 40ng/mouse, i.c.v.) dose dependently antagonized the effects of CRF (0.3nmol/mouse, i.c.v.) in social interaction and forced swim test. CRF antagonist [alpha-Helical CRF (9-41), (1 or 10nmol/mouse, i.c.v.)] was found to exhibit anxiolytic- and antidepressant-like effect, and its sub-effective dose (0.1nmol/mouse, i.c.v.) when administered along with sub-threshold dose of leuprolide (10ng/mouse, i.c.v.), or d-Trp-6-LHRH (20ng/mouse, i.c.v.) also produced significant anxiolytic- and antidepressant-like effect. These observations suggest reciprocating role of GnRH in modulating the CRF induced anxiogenic- and depressant-like effects.
Gynecol Oncol. 2008 May 27;
Schonman R, Klein Z, Edelstein E, Czernobilsky B, Fishman A
BACKGROUND: Luteinized thecoma of the ovary associated with sclerosing peritonitis is a rare tumor that has no standard definitive treatment regimen. CASE: A 25 year-old patient diagnosed with luteinized thecoma and sclerosing peritonitis in the omentum. The patient received high dose corticosteroids (IV Hydrocortisone 500 mg/d) and GnRH agonist (IM Leuprolide 3.75 mg) in order to achieve ovarian suppression and relief of the clinical peritonitis. She was re-admitted two weeks later due to bowel obstruction which was treated conservatively. The steroid regimen was continued by oral intake for 5 weeks with complete remission of the peritonitis related symptoms. The bilateral enlarged ovarian tumor-like solid was the prominent finding in consecutive ultrasound exams with no decrease in size despite of the above mentioned protocol. Thus, the patient was re-operated for exploration and biopsies of the ovary and the pathology report showed no evidence of remnant disease in the ovary, or in the peritoneum. Completing follow-up of 15 months since the last operation, the patient is asymptomatic. She conceived spontaneously and currently is in her 24th week of a normal pregnancy. CONCLUSION: This is the first case report in the English literature of a successful medical conservative treatment of a young patient with luteinized thecoma associated with sclerosing peritonitis that led to complete relief of the symptoms and allowed fertility preservation.
Clin Genitourin Cancer. 2008 Mar; 6(1): 46-52
Bruchovsky N, Klotz L, Crook J, Phillips N, Abersbach J, Goldenberg SL
BACKGROUND: Observations of quality of life (QOL), morbidity, and mortality were obtained from the results of a prospective phase II study of intermittent androgen suppression for recurrent prostate cancer after radiation therapy. PATIENTS AND METHODS: Patients with histologically confirmed adenocarcinoma of the prostate and a rising serum prostate-specific antigen level after external-beam radiation of the prostate were treated intermittently with a 36-week course of cyproterone and leuprolide. At predetermined intervals, QOL was assessed using the Southwest Oncology Group 9346 QOL and the American Urological Association symptom score questionnaires. Progression-free and overall survival rates were estimated using the Kaplan-Meier method. Parameters related to progression were explored with univariate and multivariate analyses. RESULTS: The incidence of adverse events was higher when patients were on treatment. Fatigue, dyspnea, and hematuria were the most common symptoms and signs recorded (50.5%, 24.8%, and 17.4%, respectively). Less frequent were myocardial infarction (7.3%), cerebrovascular accident (6.4%), and deep vein thrombosis (5.5%). Quality of life improved when off treatment, as indicated by a shift toward baseline levels in the scales depicting physical and work functions, hot flashes, impotence, sexual performance, urgency, and nocturia. Biochemical recurrence-free survival at 5 years was 70%, with a median > 6 years. The overall 5-year survival was 80%, similar to that of an age-matched population of normal men. CONCLUSION: Intermittent androgen suppression is a potentially useful treatment for locally recurrent prostate cancer after radiation therapy with QOL benefits in the off-treatment interval and no apparent deleterious effects on short- to medium-term survival.
J Pharm Sci. 2008 May 20;
Astaneh R, Erfan M, Moghimi H, Mobedi H
The effects of polymer molecular weight on drug release behavior would be more complicated from in situ forming implants (ISFIs) that change gradually from liquid to semi-solid or solid after injection. To investigate this phenomenon, three commercially available D,L-lactic acid-co-glycolic acid (PLGA) polymers with molecular weights of 12, 34, and 48 kDa were used to prepare ISFIs containing leuprolide acetate (LA) as a model peptide. The influence of polymer molecular weight on the membrane formation, morphology, and also on their in vitro drug release behavior over a period of 28 days was investigated. Results showed that the amount of drug released over the first 24 h (36% +/- 0.34%) (burst release), for formulation prepared with polymer RG 503H (medium molecular weight, M(w) 34 kDa), was significantly higher than others (p < 0.05). Surface and cross-section morphology of ISFI prepared with medium molecular weight polymer to cellular and spongy-like structure which was in good agreement with the release behavior of LA from it. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.
New approaches to the therapy of various tumors based on Peptide analogues.
Horm Metab Res. 2008 May; 40(5): 315-22
Schally AV
The discovery of hypothalamic hormones was briefly reviewed. The development of new hormonal methods for the therapy of various cancers based on analogues of hypothalmic hormones is then presented. My group isolated luteininzing hormone-releasing hormone (LH-RH), also known as Gn-RH, from pig hypothalmi, elucidated its amino acid sequence, and synthesized it in 1971. The interest in medical applications of LH-RH led to the synthesis of LH-RH analogues by various groups. LH-RH agonists substituted in positions 6 or 10 including Decapeptyl, Leuprolide and Zoladex are much more active than LH-RH and on continuous administration produce inhibition of pituitary and gonads. Chronic administration of LH-RH agonists is being utilized for the treatment of prostate and breast cancer. Octapeptide analogues of somatostatin have various applications in Oncology. In 1980 we developed a new endocrine therapy for advanced prostate cancer based on agonists of LH-RH, which is now preferred by 70-90% of prostate cancer patients for primary treatment. LH-RH antagonists such as Cetrorelix can be used for therapy of BPH. On the basis of the presence of specific receptors for hypothalamic peptides on human cancers, we developed targeted cytotoxic analogues of LH-RH, somatostatin, and bombesin/GRP linked to doxorubicin or 2-pyrrolinodoxorubicin. These analogues inhibit the growth of experimental human prostate, breast, ovarian and endometrial cancer, renal cell carcinoma, pancreatic, colorectal and gastric cancers, small cell lung carcinoma (SCLC) and non-SCLC, brain tumors, melanomas, and lymphomas. Cytotoxic LH-RH analogues are now in clinical trials. Recently we demonstrated that growth hormone-releasing hormone (GH-RH) also serves as an autocrine growth factor in many cancers. Antagonistic analogues of GH-RH synthesized in our laboratory inhibit the growth of diverse tumors. The discovery of LH-RH and somatostatin has led to clinical use of their analogues in the field of cancer treatment and GH-RH antagonists also show a great promise.
AAPS J. 2004; 6(1): 45-56
Arulsudar N, Subramanian N, Mishra P, Chuttani K, Sharma RK, Murthy RS
The purpose of this study was to prepare conventional and sterically stabilized liposomes containing leuprolide acetate in an attempt to prolong the biological half life of the drug, to reduce the uptake by reticuloendothelial system (RES), and to reduce the injection frequency of intravenously administered peptide drugs. The conventional and sterically stabilized liposomes containing leuprolide acetate were prepared by reverse phase evaporation method and characterized for entrapment efficiency and particle size. Radiolabeling of leuprolide acetate and its liposomes was performed by direct labeling with reduced technetium-99m. Its biodistribution and imaging characteristics were studied in ehrlich ascites tumor (EAT)-bearing mice after labeling with technetium-99m. The systemic pharmacokinetic studies were performed in rabbits. A high uptake by tumor was observed by sterically stabilized liposome containing leuprolide acetate compared with free drug and conventional liposomes. The liver/tumor uptake ratio of free drug, conventional (LL), and sterically stabilized liposomes (SLL5000 and SLL2000) was found to be 20, 7.99, 1.63, and 1.23, respectively, which showed the increased accumulation of sterically stabilized liposomes in tumor compared with the free drug and conventional liposomes at 24 hours postinjection. Liver uptake of sterically stabilized liposomes was still 7-fold less than the conventional liposomes. The marked accumulation of liposomes in the tumor-bearing mice was also documented by gamma scintigraphic studies. The findings demonstrate the distribution of these liposomes within solid tumor and prove that the sterically stabilized liposomes experience increased tumor uptake and prolonged circulation half life. Hence these findings will be relevant for the optimal design of long circulating liposomes for the peptide drugs and for targeting of liposomes toward tumor.
Can J Cardiol. 2008 May; 24(5): 401-3
Basarici I, Belgi A, Yalcinkaya S
A 35-year-old woman with a previously repaired atrial septal defect was referred for preoperative evaluation before laparoscopic surgery. The patient was asymptomatic, and a transesophageal echocardiographic examination revealed a probable thrombus attached to the tricuspid valve. The patient's history included therapy with a gonadotropin-releasing hormone analogue and deep venous thrombosis five months earlier. The tricuspid valve thrombus disappeared after anticoagulant therapy. Warfarin was initiated for prophylaxis. During the follow-up, the patient was event-free during laparoscopic surgery and pregnancy (when warfarin was switched to acetylsalicylic acid) and gave birth to a healthy term baby. Because etiological investigations revealed no reason for the tricuspid valve thrombus, it was considered to be related to the procoagulant state induced by hormonal treatment. The patient was scheduled for close follow-up.