trelstar and Adenocarcinoma

The development of resistance to anticancer therapies is a major hurdle in preventing long-lasting clinical responses to conventional therapies in hormone-refractory prostate cancer. Herein, the molecular evidence documenting that bone metastasis microenvironment survival factors (mainly the paracrine growth hormone-independent, urokinase-type plasminogen activator-mediated increase of IGF-1 and the endocrine production of growth hormone-dependent IGF-1, mainly liver-derived IGF-1 production) produce an epigenetic form of prostate cancer cells that are resistant to proapoptotic therapies is reviewed. Consequently, the authors present the conceptual framework of a novel antibone microenvironment survival factor, mainly an anti-IGF-1 hormonal manipulation for androgen ablation refractory prostate cancer (a combination of conventional androgen ablation therapy [luteinising hormone-releasing hormone agonist-A or orchiectomy]) with dexamethasone plus somatostatin analogue, which yielded durable objective responses and major improvement of bone pain and performance status in stage D3 prostate cancer patients.

Topics: Adenocarcinoma; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Bone Neoplasms; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Dexamethasone; Drug Resistance, Neoplasm; Estramustine; Etoposide; Gonadotropin-Releasing Hormone; Growth Substances; Humans; Leuprolide; Male; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Orchiectomy; Osteoblasts; Osteoclasts; Paracrine Communication; Peptides, Cyclic; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Receptors, Androgen; Salvage Therapy; Somatostatin; Survival Analysis; Triptorelin Pamoate

A case is reported of a poorly differentiated hepatocellular carcinoma that occurred in a 65-year-old patient who was on hormonotherapy for prostatic adenocarcinoma. The diagnosis of hepatocellular carcinoma was made 3 months after the initiation of a hormonal treatment with cyproterone acetate (for 1 month) and an LH-RH agonist. A cause and effect relationship between steroid hormones and hepatocellular carcinoma has been advocated in the literature. The occurrence of hepatic malignancy after a short hormonal therapy makes our case very unusual.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cyproterone Acetate; Humans; Liver Neoplasms; Male; Neoplasms, Second Primary; Prostatic Neoplasms; Triptorelin Pamoate

Few randomised studies have compared antiandrogen intermittent hormonal therapy (IHT) with continuous maximal androgen blockade (MAB) therapy for advanced prostate cancer (PCa).. To determine whether overall survival (OS) on IHT (cyproterone acetate; CPA) is noninferior to OS on continuous MAB.. This phase 3 randomised trial compared IHT and continuous MAB in patients with locally advanced or metastatic PCa.. During induction, patients received CPA 200 mg/d for 2 wk and then monthly depot injections of a luteinising hormone-releasing hormone (LHRH; triptoreline 11.25 mg) analogue plus CPA 200 mg/d. Patients whose prostate-specific antigen (PSA) was <4 ng/ml after 3 mo of induction treatment were randomised to the IHT arm (stopped treatment and restarted on CPA 300 mg/d monotherapy if PSA rose to ≥20 ng/ml or they were symptomatic) or the continuous arm (CPA 200 mg/d plus monthly LHRH analogue).. Primary outcome measurement was OS. Secondary outcomes included cause-specific survival, time to subjective or objective progression, and quality of life. Time off therapy in the intermittent arm was recorded.. We recruited 1045 patients, of which 918 responded to induction therapy and were randomised (462 to IHT and 456 to continuous MAB). OS was similar between groups (p=0.25), and noninferiority of IHT was demonstrated (hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.76-1.07). There was a trend for an interaction between PSA and treatment (p=0.05), favouring IHT over continuous therapy in patients with PSA ≤1 ng/ml (HR: 0.79; 95% CI, 0.61-1.02). Men treated with IHT reported better sexual function. Among the 462 patients on IHT, 50% and 28% of patients were off therapy for ≥2.5 yr or >5 yr, respectively, after randomisation. The main limitation is that the length of time for the trial to mature means that other therapies are now available. A second limitation is that T3 patients may now profit from watchful waiting instead of androgen-deprivation therapy.. Noninferiority of IHT in terms of survival and its association with better sexual activity than continuous therapy suggest that IHT should be considered for use in routine clinical practice.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cyproterone Acetate; Disease Progression; Europe; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Sexuality; Survival Rate; Time Factors; Triptorelin Pamoate

To evaluate the efficacy and safety of administering a 3-month formulation of triptorelin as part of disease management of Taiwanese men with advanced adenocarcinoma of the prostate.. Patients with newly diagnosed, locally advanced, or metastatic adenocarcinoma of the prostate were enrolled in our study, after informed consent was obtained. All patients received bicalutamide 50 mg daily for 28 days, starting 7 days before the first injection of triptorelin. A dosage of 11.25 mg triptorelin was injected on Day 0 (baseline) and repeated on Day 90. Prostate-specific antigen (PSA) and testosterone concentrations were measured on Days 90 and 180.. A total of 41 patients were enrolled, with a median age of 78 (57-92) years, and a baseline median PSA of 122.69 ng/mL. One patient dropped out of the study, one was excluded in the fourth month due to a protocol violation, and one died 4 months after initiation of treatment as a result of disease progression. In total, 40 men were eligible for Day 90 and 38 men for Day 180 analysis. On Day 90, 97.5% of men had reached castration testosterone concentration ≤0.5 ng/mL, and all men had reached this concentration on Day 180. Serum PSA concentration declined to 10.40 ± 23.42 ng/mL on Day 90 (p = 0.0126) and 11.61 ± 23.93 ng/mL on Day 180 (p = 0.0172). The most frequently seen adverse event was gastrointestinal disturbance, including abdominal pain, diarrhea and constipation. Generally, adverse events were mild and patient manageable.. Triptorelin 11.25 mg is effective in achieving medical castration and lowering PSA concentrations and can maintain its medicinal effect for at least 90 days in Taiwanese men with advanced prostate cancer. This suggests that it can be an effective treatment for advanced prostatic cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.. Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng/mL, Gleason score≥7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival.. The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2.. No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease-Free Survival; Drug Administration Schedule; Flutamide; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Conformal; Risk Factors; Treatment Outcome; Triptorelin Pamoate

To evaluate prospectively the combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone in patients with hormone-refractory prostate cancer (HRPC) in a randomized Phase II study. HRPC presents a challenging therapeutic problem. Salvage chemotherapy is the usual approach at this stage of the disease. The combination of a luteinizing hormone-releasing hormone analog with a somatostatin analog and dexamethasone has produced objective clinical responses in HRPC.. Forty patients with HRPC were randomized to receive one of two treatments. Group 1 underwent chemotherapy (estramustine 140 mg three times daily and etoposide 100 mg orally for 21 days) and group 2 the combination of a somatostatin analog (lanreotide 30 mg intramuscularly every 14 days) and dexamethasone (4 mg tapered to 1 mg), in addition to androgen ablation by orchiectomy or a luteinizing hormone-releasing hormone analog (triptorelin 3.75 mg intramuscularly every 28 days). The clinical and prostate-specific antigen (PSA) response, overall survival, time to progression, and toxicity were compared between the two groups.. The data of 20 patients in group 1 and 18 in group 2 were analyzed. The demographic and clinical data were similar in the two groups at study entry. A PSA response (decrease of greater than 50%) was observed in 45% of group 1 and 44% of group 2. The difference was not statistically significant. A partial clinical response was observed in 29% and 30% of groups 1 and 2, respectively. Again, the difference was not statistically significant. Changes in performance status and pain score during treatment were not significantly different in the two groups. Hematologic toxicity was more frequent in group 1 (80% of patients), and mild diabetes was more frequent in group 2 (22% of patients). The overall survival was 18.8 months in group 1 and 18 months in group 2 (not statistically significant). The time to progression was 6 versus 4 months and, in the PSA responder subgroup, it was 8 versus 7.7 months in groups 1 and 2, respectively (neither difference was statistically significant).. The results of our randomized Phase II study indicated that the new combination treatment (luteinizing hormone-releasing hormone analog, somatostatin analog, and dexamethasone) may be equally effective as salvage chemotherapy in patients with HRPC in terms of the clinical and PSA response, overall survival, and time to progression. A larger prospective Phase III trial is required to confirm our observations.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Dexamethasone; Diabetes Mellitus; Disease-Free Survival; Estramustine; Etoposide; Gastrointestinal Diseases; Gonadotropin-Releasing Hormone; Hematologic Diseases; Humans; Life Tables; Male; Middle Aged; Orchiectomy; Peptides, Cyclic; Prostatic Neoplasms; Somatostatin; Survival Analysis; Treatment Outcome; Triptorelin Pamoate

To determine whether the administration of the nonsteroidal antiandrogen bicalutamide reduces the risk of an increase in chromogranin A (CgA) levels in patients with prostate cancer who experienced biochemical failure after radical retropubic prostatectomy (RRP) compared with pharmacologic castration therapy. It has been hypothesized that continuous androgen suppression for the treatment of prostate cancer results in hyperactivation of neuroendocrine cells and an increase in CgA levels.. Forty-eight patients with pT3pN0M0 prostate cancer and biochemical (prostate-specific antigen) progression after RRP were randomized to bicalutamide monotherapy or pharmacologic castration. The serum levels of CgA and prostate-specific antigen were measured at 1, 3, 6, 12, 18, and 24 months of therapy. The changes in serum CgA levels were compared for patients who successfully responded to the first 24 months of therapy.. In both treatment groups, a statistically significant trend was noted for CgA levels to increase from baseline to 24 months. This trend was lower in the bicalutamide group (slope = 0.60, 95% confidence interval 0.28 to 0.92; P = 0.004) than in the castration group (slope = 0.29, 95% confidence interval 0.08 to 0.50; P = 0.01).. The results of this study provide the first evidence to show that in patients with prostate cancer undergoing hormonal therapy, nonsteroidal antiandrogen monotherapy produces a significantly lower increase in serum CgA compared with castration.

Topics: Adenocarcinoma; Aged; Androgens; Anilides; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Cell Differentiation; Chromogranin A; Chromogranins; Disease Progression; Gonadotropin-Releasing Hormone; Humans; Lymph Node Excision; Male; Middle Aged; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Neurosecretory Systems; Nitriles; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Tosyl Compounds; Triptorelin Pamoate

It has been hypothesized that continuous androgen-suppression therapy produces hyperactivation of neuroendocrine (NE) cells and an increase in chromogranin A (CgA) in prostate carcinoma (PC). The aim of this study was to verify whether the intermittent administration of androgen deprivation (IAD) reduces the risk of CgA increase in PC cases treated with complete androgen deprivation (CAD).. We analyzed changes in serum CgA levels in patients with PC who successfully responded to the first 24 months of IAD versus continuous CAD therapy. Two different populations were analyzed: Type 1 = pT3pN0M0 prostate cancers with biochemical (PSA) progression after RRP; Type 2 = metastatic PC directly submitted to CAD. Cases in Type 1 and Type 2 population were randomly assigned to IAD versus continuous CAD therapy. Forty cases each in Type 1 and Type 2 population were included in the analysis. At 1, 3, 6, 12, 18, 24 months of IAD versus continuous therapy, serum levels of CgA compared to PSA levels were analyzed.. In population Type 1 and Type 2, in the group of cases continuously treated with CAD (Group 2), there was a significant trend to increase for CgA levels from baseline to 24 months of therapy. On the contrary, no significant variations were found in cases treated with IAD (Group 1). Either in population Type 1 or Type 2, at 12- and 24-month follow-up, mean and median serum levels of CgA were significantly (P < 0.005) lower in Group 1 than in Group 2.. The present study represents the first evidence in the literature that the intermittent administration of CAD therapy significantly reduces the increase in serum CgA levels during CAD therapy.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chromogranin A; Chromogranins; Flutamide; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Triptorelin Pamoate

We evaluate the relationship between the use of synthetic gonadotropin-releasing hormone (Gn-RH) agonists and bone loss in men.. Bone mineral density and parameters of mineral metabolism were evaluated in 12 patients with stage C prostatic carcinoma before and after 6, 12 and 18 months of treatment with 3.75 mg. triptorelin intramuscularly every 4 weeks.. Of the 12 patients 9 were evaluated after 6, 7 after 12 and 6 after 18 months of therapy. In comparison with month 0, the lumbar and femoral neck bone mineral density tended to decrease at month 6 (-3 and -2.7%, p = 0.31 and 0.17, respectively), at month 12 (-4.6 and -3.9%, p = 0.13 and 0.13) and at month 18 (-7.1 and -6.6%, p = 0.12 and 0.027). A second analysis revealed that the lumbar and femoral neck bone mineral density was significantly decreased on the last evaluation compared to month 0 (p = 0.05 and 0.028, respectively). The serum osteocalcin was increased during treatment, suggesting an accelerated bone turnover in men treated with Gn-RH agonists.. The use of Gn-RH agonists in men may induce an accelerated bone loss. Further studies are needed to confirm these results and to evaluate the incidence of osteoporotic fractures in men treated with Gn-RH agonists.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Bone Density; Humans; Male; Prostatic Neoplasms; Time Factors; Triptorelin Pamoate

The pharmacodynamics and the pharmacokinetic characteristics of a new longer-acting formulation containing 11.25 mg of triptorelin (Decapeptyl) to be administered every 3 months were evaluated in 14 patients with advanced prostate carcinoma. After one single injection, the mean time to reach the surgical castration testosterone range is 22 days, and this effective testosterone suppression is maintained for the 3-month therapy. After a first plasma surge (35.70 ng/ml) occurring 2.5 h after injection and a rise between day 17 and day 31 (maximum on day 24: 0.32 ng/ml), the mean triptorelin plasma level is stable (0.06 +/- 0.05 ng/ml) and maintained until day 91. This new formulation was well tolerated both locally and systemically.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Follicle Stimulating Hormone; Humans; Kinetics; Luteinizing Hormone; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Comparative efficacy and safety of 2 LHRH analogues in metastatic prostatic carcinoma.. 68 patients received monthly injections for 6 months (randomization): either subcutaneous leuprolide 3.75 mg LP (n = 36), or intramuscular triptorelin 3.75 mg LP (n = 32). (Flare-up prevention: nilutamide). Parameters re-evaluated at 1.3 and 6 months: centralized assays of plasma testosterone (T), LH and serum PSA; clinical symptoms. Main criterion: proportion of patients with T < or = 0.5 ng/mL.. The percentages of patients with T < or = 0.50 ng/mL was not significantly different between the two groups and were equal to 100 and 90%, 97 and 100%, and 100 and 96% at the 3 study times, for leuprolide or triptorelin, respectively. The difference was significant at 1 month on complementary analysis at the limit of T < 0.30 ng/mL: 86% with leuprolide versus 60% with triptorelin (p = 0.02) and for mean plasma testosterone: 0.16 +/- 0.10 ng/mL versus 0.33 +/- 0.44 ng/mL, respectively (p = 0.02). The clinical subjective efficacy was not significantly different.. Both treatments were effective, although plasma testosterone fell more rapidly with leuprolide. No conclusion about the possible clinical or survival benefits can be formulated. Overall safety was satisfactory.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Data Interpretation, Statistical; Drug Tolerance; Humans; Imidazoles; Imidazolidines; Injections, Intramuscular; Injections, Subcutaneous; Leuprolide; Male; Middle Aged; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Time Factors; Triptorelin Pamoate

Between 1987 and 1989 we treated 18 patients with advanced pancreatic adenocarcinoma with a long acting LH-RH analogue: triptorelin. Seventeen patients were evaluated. We obtained no objective responses. The median survival time was 4.5 months. The treatment was well tolerated without any major secondary effects. The absence of dosage of hormonal receptors did not allow the selection of hormone sensitive patients. The future study of hormone therapy will analyse the pancreatic hormonal receptors.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Female; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Pancreatic Neoplasms; Triptorelin Pamoate

Three major assumptions emerged from these clinical and endocrine long-term studies. First, buserelin, given pernasally in the conventional doses, and Decapeptyl microcapsules administered intramuscularly in 5-week intervals are equally effective in terms of their long-term castration effect in previously untreated patients with prostatic carcinoma. However, Decapeptyl causes complete LH and subsequent testosterone down-regulation 1 week earlier than buserelin. Furthermore, this treatment is more convenient, and the compliance is better. Both LHRH analogues are equally well tolerated. Second, in groups of prostate cancer patients with far advanced disease treated with palliative intention, only true subjective or objective remission should be considered a positive treatment response. Third, our results comparing PAP and PSA as the two most useful tumor markers with the corresponding testosterone levels suggest a close correlation.

Topics: Adenocarcinoma; Administration, Intranasal; Antineoplastic Agents; Biomarkers, Tumor; Buserelin; Clinical Trials as Topic; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Lymphatic Metastasis; Male; Neoplasm Staging; Prostatic Neoplasms; Time Factors; Triptorelin Pamoate

Squamous cell carcinoma of the prostate is rare and represents 0.5% to 1% of prostatic carcinomas. Transformation of prostatic adenocarcinoma into squamous cell carcinoma after LH-RH agonist intake has been reported in only 8 cases in the literature. To our knowledge, our case is the second pure squamous cell carcinoma observed after hormonotherapy and radiotherapy. We reported a case of a patient with prostatic adenocarcinoma treated by radical prostatectomy followed by radiotherapy. Eleven years later, he had a vesical recurrence of prostatic adenocarcinoma. Our patient had an endoscopic resection followed by injections of Triptorelin. Six months later, he developed a local recurrence of a squamous cell carcinoma.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Carcinoma, Squamous Cell; Combined Modality Therapy; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasm Recurrence, Local; Prostatectomy; Prostatic Neoplasms; Triptorelin Pamoate

Primary seminal vesicle adenocarcinoma is one of the rarest genitourinary cancers. The pathogenesis is unknown and clinical manifestations are protean. There is no defined treatment for this disease and various combinations of surgery, chemotherapy, radiation therapy and hormonal therapy have been used in the past. Here, we have reported a primary seminal vesicle adenocarcinoma with hepatic metastases, managed with multiagent chemotherapy (oxaliplatin and 5-fluorouracil based) and androgen ablation (with triptorelin). The key to management of such a case is early diagnosis and multimodal treatment. The reported survival rate continues to be poor even for a localised disease. A consolidated follow-up protocol ensures early diagnosis of recurrent or metastatic disease so that second-line therapy can be started.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Fluorouracil; Genital Neoplasms, Male; Humans; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Seminal Vesicles; Triptorelin Pamoate

Topics: Adenocarcinoma; Adenoma; Aged; Antineoplastic Agents, Hormonal; Diplopia; Headache; Humans; Hypophysectomy; Magnetic Resonance Imaging; Male; Neoplasms, Multiple Primary; Neoplasms, Unknown Primary; Pituitary Apoplexy; Pituitary Neoplasms; Prostatic Neoplasms; Triptorelin Pamoate

Androgen-deprivation therapy (ADT) has been reported to be active in androgen receptor (AR)-expressing, relapsed/metastatic (RM), salivary gland cancers (SGCs). Abiraterone, an inhibitor of androgen synthesis, has recently been approved as a second-line treatment in hormone-resistant (HR) prostate cancer (PCa) patients. Two patients with AR-positive HR-RM adenocarcinoma, NOS of the salivary glands have been treated with abiraterone. This is the first time that this agent has been reported to be active in tumors other than HRPCa. Immunohistochemical analysis showed overexpression of EGFR, HER2, and HER3 in both untreated primary tumors. Sequencing analysis revealed a TP53 non-functional mutation in one case and a PIK3CA-activating mutation in the other. In conclusion, second line activity of ADT in AR-expressing, adenocarcinoma, NOS of salivary glands further strengthens the pathogenic and therapeutic role of AR signaling in AR-positive SGCs.

Topics: Adenocarcinoma; Adult; Androgen Antagonists; Androstenes; Androstenols; Anilides; Antineoplastic Agents, Hormonal; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms, Hormone-Dependent; Nitriles; Receptors, Androgen; Salivary Gland Neoplasms; Tosyl Compounds; Treatment Outcome; Triptorelin Pamoate

This study has aimed to analyze the changes observed in the lipid profile and atherogenic risk in prostate cancer patients subjected to androgen deprivation.. Between 2001 and 2008, serum lipoproteins (total cholesterol, HDL, LDL and triglycerides) were determined in 636 patients. Of these, 129 were treated with maximum androgen blockade and 177 patients were only treated with LHRH analogue. The control group was formed by 339 subjected to prostate biopsy (212 with prostate cancer and 127 without prostate cancer). The atherogenic risk was calculated using the Castelli formula (total cholesterol/HDL).. Mean atherogenic risk was 4.2 in the control group and 4 in the group of patients subjected to androgenic deprivation, p>0.05. The mean atherogenic risk in those subjected to monotherapy with LHRH analogues was 4.1 while it was 3.9 in patients subjected to maximal androgen blockade, p=0.02. We did not found significant differences for atherogenic risk according to length of treatment, p>0.05. The multivariate analysis confirmed that the treatment modality was the only significant variable influencing atherogenic risk.. This study demonstrates that continuous androgen deprivation does not increase atherogenic risk in patients with prostate cancer. This risk also did not increase during the treatment. The association of bicalutamide to the LHRH analogue seems to have a protective effect on atherogenic risk.

Topics: Adenocarcinoma; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Atherosclerosis; Biopsy; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Combined Modality Therapy; Gonadotropin-Releasing Hormone; Humans; Lipoproteins; Male; Nitriles; Prostate; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Risk; Tosyl Compounds; Triglycerides; Triptorelin Pamoate

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Female; Flutamide; Humans; Incidental Findings; Leukemia, Lymphocytic, Chronic, B-Cell; Leukocyte Count; Male; Middle Aged; Neoplasms, Multiple Primary; Prostatic Neoplasms; Remission, Spontaneous; Triptorelin Pamoate

Prostate carcinoma is one of the most frecuent cancers in men. Significant numbers of patients have regional lymph node and bone metastases during the course of the disease. Mediastinal lymphadenopathy and cutaneous metastases are uncommon and signify well-advanced disease. We report the case of a patient with prostate cancer who develops mediastinal lymphadenopathy, pulmonary nodules and cutaneous metastases 8 years after the diagnosis.

Topics: Adenocarcinoma; Androgen Antagonists; Androgens; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyproterone; Diphosphonates; Estramustine; Fatal Outcome; Flutamide; Humans; Imidazoles; Ketoconazole; Lung Neoplasms; Lymphatic Metastasis; Male; Mediastinum; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Radionuclide Imaging; Skin Neoplasms; Triptorelin Pamoate; Zoledronic Acid

To prospectively assess the efficacy and tolerability of bicalutamide monotherapy on biochemical failure of localized prostate cancer following total androgen deprivation (TAD) and 3D-conformal radiotherapy (3D-CRT).. Between January 1998 and January 2002, we prospectively evaluated 20 eligible patients with biochemical failure. All patients were initially treated with neoadjuvant TAD of 12 weeks before 3D-CRT (73.6 Gy at isocenter) and same regimen of TAD after completion of radiotherapy for 24 weeks in high-risk patients. We prescribed 150 mg/day bicalutamide monotherapy for 24 weeks in patients with biochemical failure according to American Society for Therapeutic Radiology and Oncology 1997 consensus definition. Primary end points were biochemical control (BC) and metastasis-free survival (MFS).. Median follow-up was 28 months after biochemical failure date. At last visit, the median PSA level of all patients was 2.80 ng/dl while 1.28 ng/dl for nonmetastatic and 30.7 ng/dl for metastatic patients. BC was successfully obtained in five of them with only bicalutamide. Ten patients developed distant metastasis among 15 patients receiving salvage TAD. MFS was 55% at three years for all 20 patients. Temporary gynecomasty was observed in 11 patients as the only serious toxicity.. Bicalutamide monotherapy seems to be a tolerable regimen for patients with biochemical failure following 3D-CRT, and TAD and may be effective in patients with low PSA levels at biochemical failure.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Disease Progression; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nitriles; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Tosyl Compounds; Triptorelin Pamoate

To assess the factors effecting PSA bounce and to identify any possible relationship with biochemical control after 3-D conformal radiotherapy (3D-CRT) and total androgen deprivation (TAD) for prostate cancer by evaluating four previously described PSA bounce definitions.. Between January 1998 and January 2001, 83 consecutive patients with clinically localized prostate cancer were treated by 3D-CRT with neoadjuvant 3 months and/or 6 months adjuvant TAD. All patients had a pretreatment PSA level, at least eight post-external beam radiotherapy (EBRT) PSA and testosterone levels and minimum two years of follow-up. Total radiotherapy dose was 73.6 Gy at ICRU reference point. Four previous definitions of PSA bounce were used: Critz definition (>or=0.1 ng/mL), Cavanagh definition (>or=0.2 ng/mL), Hanlon definition (>or=0.4 ng/mL) and Rosser definition (>or=0.5 ng/mL) according to original methodology performed to report PSA bounce. Biochemical failure was defined in accordance with the ASTRO consensus guidelines.. The median follow-up time was 40 months. PSA bounce was recorded as follows: Critz definition, 33 patients (40%); Cavanagh definition, 21 patients (25%); Hanlon definition, 11 patients (13%); and Rosser definition, 7 patients (8%). In multivariate analysis, pre-EBRT PSA level and the duration of TAD for Critz definition; age, pre-EBRT PSA and the duration of TAD for Cavanagh definition; age and duration of TAD for Hanlon definition; age and pre-biopsy PSA for Rosser definition were significant independent prognostic factors determining PSA bounce. A significant increase of mean testosterone level in bouncers was detected at the 6th-9th and 18th-21st months. PSA bounce did not predict for PSA failure in multivariate analysis.. We observed no correlation between biochemical failure and PSA bounce. The longer duration of TAD and older age were found to be inversely proportional with PSA bouncing in this cohort. Notably, recovery of testosterone might cause PSA bouncing.

Topics: Adenocarcinoma; Aged; Androgens; Antineoplastic Agents, Hormonal; Disease Progression; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Regression Analysis; Retrospective Studies; Testosterone; Time Factors; Treatment Outcome; Triptorelin Pamoate

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Drug Therapy, Combination; Follow-Up Studies; Humans; Male; Neoplasm Recurrence, Local; Nitriles; Parotid Gland; Parotid Neoplasms; Radiotherapy, Adjuvant; Receptors, Androgen; Risk Assessment; Skin Ulcer; Tosyl Compounds; Treatment Outcome; Triptorelin Pamoate

Expression of luteinizing hormone-releasing hormone (LHRH) and its receptor as part of an autocrine regulatory system of cell proliferation has been demonstrated in a number of human malignant tumors, including cancers of the ovary. This study was conducted to investigate whether LHRH induces activation of JunD and affects cell cycle regulation and DNA synthesis. Treatment of primary human ovarian cancer cells and human ovarian cancer cell lines EFO-21 and EFO-27 with LHRH agonist triptorelin (100 nM) resulted in an increase in G(0/1) phase and a decrease in G(2/S) phase of cell cycle. Treatment of quiescent EFO-21 or EFO-27 cells with triptorelin (100 nM) resulted in a 46.7 or 44.2-fold increase of AP-1 activation, respectively (p<0.001). Maximal binding of JunD on DNA consensus sequence was found after 4 h of treatment of quiescent EFO-21 or EFO-27 cells with triptorelin (100 nM). DNA synthesis was significantly decreased to 45.5+/-11.4% (day 0=control=100%; p<0.001) after 3 days of triptorelin (1 nM) treatment. These results suggest that LHRH agonist triptorelin induces JunD-DNA binding, resulting in reduced proliferation as indicated by increased G(0/1) phase of cell cycle and decreased DNA synthesis. Since LHRH activates nucleus factor kappa B (NF kappa B) and protects ovarian cancer cells from doxorubicin-induced apoptosis and JunD is shown to decrease cell cycle and cell proliferation, we propose that JunD activated by LHRH acts as a modulator of cell proliferation and cooperates with the anti-apoptotic and anti-mitogenic functions of LHRH.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Apoptosis; Cell Cycle; DNA; DNA Replication; DNA, Neoplasm; Female; Flow Cytometry; Gonadotropin-Releasing Hormone; Humans; Ovarian Neoplasms; Proto-Oncogene Proteins c-jun; Triptorelin Pamoate; Tumor Cells, Cultured

To investigate whether chlormadinone acetate (CMA) could prevent the flare-up phenomenon induced by a luteinizing hormone-releasing hormone analogue (LH-RHa), we treated 4 cases of stage C and 17 cases of stage D prostate cancer with CMA for 4 weeks and CMA plus monthly injection of LH-RHa for following 24 weeks. Serum LH, testosterone, and prostate-specific antigen (PSA) levels were closely monitored before and 3 days, 1-, 2-, and 4-weeks after LH-RHa injection. Subjective and objective responses were also investigated. Serum LH and testosterone levels significantly elevated 3 days after the initial injection of LH-RHa. However, they resumed 1 week after LH-RHa injection with fluctuation under the normal range. Out of 21 cases, 3 cases (14%) consisting of 2 poorly and 1 moderately differentiated adenocarcinoma showed increased serum PSA levels 1 week after LH-RHa injection in spite of suppressed serum testosterone levels. The objective response of these 2 poorly differentiated cases was progressive disease at 24 weeks. No cases indicated worsening of clinical symptoms concerning flare-up phenomenon. CMA seemed to be capable of preventing flare-up phenomenon in advanced prostate cancer.

Topics: Acute-Phase Reaction; Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Chlormadinone Acetate; Drug Therapy, Combination; Humans; Luteinizing Hormone; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

We report endometrial adenocarcinoma in two patients shortly after suspending GnRH-agonist treatment for menometrorrhagia and uterine fibromata.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Female; Humans; Injections, Intramuscular; Leiomyoma; Leuprolide; Metrorrhagia; Middle Aged; Myometrium; Neoplasms, Second Primary; Triptorelin Pamoate; Uterine Neoplasms

The authors report an extremely rare case of adenoid cystic carcinoma of the prostate. No satisfactory clinical and pathological classification exists for this tumour, creating particular difficulties for therapeutic decisions and prognosis. Descriptions of cases with excellent survival rates are reported in the literature, to the extent that this is sometimes regarded as a low-malignancy tumour, but other reports also exist of massive diffusion of the pathology with fatal consequences. Advances in the knowledge of this tumour have enabled a number of earlier pathogenetic hypotheses to be ruled out, namely its possible derivation from ectopic salivary cells, ectopic periurethral glands or metaplastic urethral mucosa, but the origin of this carcinoma is still not certain. It is also difficult to differentiate this form from the typical adenocarcinoma and to make a prognosis for survival. In the case reported here, the final diagnosis was made on the lymph node biopsy obtained during surgery, given that a preoperative biopsy was not feasible owing to the scarcity of material available. The patient received standard hormonal therapy for prostate carcinoma.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Biopsy; Carcinoma, Adenoid Cystic; Diagnosis, Differential; Flutamide; Gonadotropin-Releasing Hormone; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Triptorelin Pamoate

We report a study in which our objective was to analyze the clinical response during IAD in patients with biochemical failure after RRP for clinically localized prostate cancer. Between February 1994 and May 1996, 34 patients who exhibited a primary postoperative decrease in PSA to below the detection limit after RRP and then showed PSA progression during follow-up were included as group 1 and 17 patients in whom PSA did not decrease after RRP were included as group 2. Patients were offered IAD when PSA progressed over 0.4 ng/ml in group 1 and over 4.0 ng/ml in group 2. Median follow-up is 184 weeks in group 1 and 206 weeks in group 2. The median time "off" therapy increased from 25% (1st cycle) to 68.7% (5th cycle) of the entire cycle in group 1 and from 33.3% to 58.3% in group 2. Nine out of 12 cases with Gleason score > or =8 failed to respond to IAD and all developed metastatic and/or local failure. No case with Gleason score <7 failed to respond to IAD. Our conclusions suggest that IAD may be effective in patients with biochemical progression after RRP. In our experience, Gleason score seems to be an important variable.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyproterone Acetate; Humans; Lymph Nodes; Male; Middle Aged; Postoperative Care; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Treatment Outcome; Triptorelin Pamoate

To examine the involvement of insulin-like growth factors (IGFs) in growth regulation of an ovarian cancer cell line and to investigate whether the GnRH agonist tryptorelin might influence a potential autocrine or paracrine loop involving IGFs.. In vitro, prospective, randomized controlled study.. In vitro experiments at the Section of Gynecologic Oncology, Surgery Branch, National Cancer Institute.. None. Human ovarian adenocarcinoma cell line IGROV-1.. The proliferative effect of tryptorelin on IGROV-1 cells was analyzed by using the MTT (93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) colorimetric assay. The ribonuclease protection assay was used to investigate whether an autocrine pathway involving IGF-I or IGF-II might participate in the growth of these cells. The expression of GnRH receptor was assessed by the 125I-GnRH binding assay.. Changes in cell growth and expression of IGF-I and IGF-II messenger RNA (mRNA).. Tryptorelin exhibited a bimodal, dose- and time-dependent effect on IGROV-1 cells when compared with untreated control cells: Cellular proliferation was enhanced during the first 24 hours of exposure, but longer incubations resulted in growth inhibition. The mitogenic effect of tryptorelin was inhibited when cells were co-incubated with either IGF binding protein-5 (IGFBP-5) or anti-IGF-II antibody, which can both bind to IGF-II and neutralize it. Insulin-like growth factor-I mRNA was not detected in IGROV-1 cells. However, IGF-II transcripts were detected after incubation with tryptorelin for 12 hours, but thereafter, no mRNA was observed, even after prolonged exposure. Binding analysis revealed a specific, high-affinity GnRH binding site.. These data suggest that tryptorelin exerts a bimodal growth effect on ovarian cancer cells by a mechanism involving the autocrine production of IGF-II. The effect of tryptorelin on IGF-II gene transcription in these ovarian cancer cells appears to mirror the desensitizing effects of prolonged GnRH exposure on pituitary gonadotropin production.

Topics: Adenocarcinoma; Antibodies; Cell Division; Female; Gene Expression; Humans; Insulin-Like Growth Factor Binding Protein 5; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Mitogens; Ovarian Neoplasms; RNA, Messenger; Triptorelin Pamoate; Tumor Cells, Cultured

Topics: Adenocarcinoma; Aged; Breast Neoplasms; Female; Humans; Lung Neoplasms; Menopause; Radiography; Triptorelin Pamoate

A case is presented of a middle-aged man suffering from stage D2 prostate cancer with pulmonary metastases who responded favorably, first, to endocrine combination therapy with the antiandrogen flutamide and an LHRH agonist for 5.5 years, and, second, to the subsequent withdrawal of Flutamide at the time of the progression of the disease. This case has several exceptional features: absence of bone metastases, pulmonary metastatic nodules characterized as focal neuroendocrine differentiation, and a positive response to antiandrogen withdrawal upon relapse of metastases after initial positive response. The concept of escape to androgen blockade and development of androgenic hypersensitivity is discussed.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Bone and Bones; Flutamide; Gonadotropin-Releasing Hormone; Humans; Lung Neoplasms; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Sputum; Tomography, X-Ray Computed; Triptorelin Pamoate

The effects of 3 months treatment with the GnRH agonist triptorelin as a neoadjuvant to total prostatectomy in 40 men with localized prostatic cancer have been evaluated. The study included 1 patient with a stage T1b tumour, 25 patients with stage T2 tumours and 14 with stage T3 tumours. The patients were examined by digital rectal examination, transrectal ultrasound before and after treatment. Serum testosterone and prostate-specific antigen (PSA) levels were followed. The totally removed prostate gland was step-sectioned at 5-mm intervals and the whole-mount sections were assessed for tumour pathology stage (pT stage). Triptorelin treatment resulted in a significant decrease in total gland and tumour volume and in a reduction in the serum levels of PSA and testosterone. In comparison with the findings from a previous study, in which neoadjuvant treatment was not used, it appears that the proportion of tumours invading the margins of the surgical specimen decreased.

Topics: Adenocarcinoma; Aged; Combined Modality Therapy; Cyproterone Acetate; Drug Therapy, Combination; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

A 75-year-old patient presented with a superior vena cava syndrome (SVCS) lasting 3 years. A prostatic carcinoma was found and a supraclavicular lymph node biopsy specimen disclosed metastasis of the prostatic carcinoma. Antiandrogen and luteinizing hormone-releasing hormone analogue therapy produced a marked improvement. Prostatic carcinoma, although a very rare cause, must be considered in the diagnosis of cases of SVCS with a protracted course, since it is a treatable disease.

Topics: Adenocarcinoma; Aged; Biopsy; Flutamide; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Prostatic Neoplasms; Superior Vena Cava Syndrome; Time Factors; Triptorelin Pamoate

Human breast carcinoma (MCF-7 MIII), which exhibits an estrogen-independent but estrogen-responsive phenotype, was xenografted in 8-9-week-old intact female athymic nude mice without estrogen supplementation. In this model, we investigated inhibitory effects of the modern luteinizing hormone-releasing hormone (LH-RH) antagonist SB-75 and the agonist D-Trp6-LH-RH. The analogs were administered in the form of sustained delivery systems (microcapsules and microgranules). In the first experiment, treatment lasted 10 weeks. After 9 weeks of treatment, a significant inhibition of tumor volume was first found only in the group treated with SB-75, but the final tumor volume was significantly suppressed both by D-Trp6-LH-RH and SB-75. In the second experiment, treatment was started 70 days after tumor transplantation and was continued for 6 weeks. Chronic treatment with SB-75 or D-Trp6-LH-RH appeared to completely arrest tumor growth as measured by tumor volume, percentage change in tumor volume, and tumor weight. Serum estradiol was suppressed to undetectable levels and LH levels were also diminished. Histologically, the regressive changes in the treated tumors were due to the enhancement of apoptosis (programmed cell death) of tumor cells. Membrane receptor assays showed that LH-RH binding sites were down-regulated in tumor cells after treatment with SB-75 or D-Trp6-LH-RH. The results indicate that the antagonist SB-75, released from sustained delivery systems, can inhibit the growth of MCF-7 MIII tumors as effectively as the agonist D-Trp6-LH-RH, but more rapidly. In view of its immediate blockade of the pituitary-gonadal axis and the absence of side effects, the LH-RH antagonist SB-75 might be considered as a possible new hormonal agent for the treatment of breast cancer.

Topics: Adenocarcinoma; Animals; Breast Neoplasms; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Incidence; Injections, Subcutaneous; Insulin-Like Growth Factor I; Luteinizing Hormone; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Hormone-Dependent; Ovariectomy; Transplantation, Heterologous; Triptorelin Pamoate; Tumor Cells, Cultured

In view of advancements in treatment of certain hormone-dependent cancers with analogues of luteinizing hormone-releasing hormone (LH-RH), this study was undertaken to establish the presence and characteristics of receptors for [D-Trp6]LH-RH on the membranes of human endometrial cancer. Specific binding of [125I,D-Trp6]LH-RH was demonstrated in membrane preparations from 24 of 31 (77%) endometrial carcinomas and from 3 of 13 (23.1%) nonmalignant human endometrial specimens. Ligand binding was dependent on temperature, time, and plasma membrane concentration in a fashion expected of a peptide hormone. Mathematical analysis of the binding data showed that interaction of [125I,D-Trp6]LH-RH with the binding sites was consistent with the presence of a single class of high affinity, noncooperative receptors (Kd 9.88 +/- 4.59 x 10(-9) M; Bmax 0.70 +/- 0.14 x 10(-12) mol/mg membrane protein). The rates of association and dissociation were calculated to be 6.5 x 10(6) M-1 min-1 and 0.021 min-1, respectively. [125I,D-Trp6]LH-RH binding was not displaced by either unlabeled somatostatin or epidermal growth factor, but was displaced completely by native LH-RH. Using 125I-epidermal growth factor, specific, high-affinity receptors were also detected in membranes from 22 of 26 (85%) endometrial cancers and in all of 6 nonmalignant endometrial specimens (Kd 0.42 +/- 0.12 x 10(-9) M; Bmax 0.30 +/- 0.15 x 10(-12) mol/mg membrane protein). The potential functional role of the receptors for [D-Trp6]LH-RH in human endometrial carcinoma is not clear, but this finding provides a rationale for the use of therapeutic approaches based on LH-RH analogues in this malignancy.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Biomarkers, Tumor; Cell Membrane; ErbB Receptors; Female; Gonadotropin-Releasing Hormone; Humans; Kinetics; Middle Aged; Receptors, LHRH; Triptorelin Pamoate; Uterine Neoplasms

Topics: Adenocarcinoma; Adult; Breast Neoplasms; Buserelin; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Femoral Neoplasms; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Male; Tamoxifen; Triptorelin Pamoate

For the past 6 years we used daily injection of luteinizing hormone-releasing hormone (LH-RH) agonists to treat patients with advanced prostate carcinoma. In this study we determined the hormonal response of the pituitary-testicular axis over a 2-month period and evaluated the safety and tolerance of the single intramuscular administration of sustained-release formulations of D-Trp-6-LH-RH microcapsules designed to release 50, 100, or 200 micrograms/day for over 1 month. Serum levels of LH, testosterone, and D-Trp-6-LH-RH were measured by RIA for up to 60 days in 10 patients with advanced prostatic carcinoma who had not received any previous drug therapy. After the administration of the microcapsules there was a biphasic increase in D-Trp-6-LH-RH serum levels. The maximal peak was obtained between 1 and 3 hr, and a second peak occurred between weeks 4 and 6. LH levels increased initially, with a maximal peak at 60 min, and elevated serum LH values persisted for more than 24 hr. LH levels began to fall on the second day, reaching subnormal values after 1 week. Serum testosterone rose during the first week and fell subsequently to less than 100 ng/dl. A rebound in LH and testosterone was seen about the 50th day after the microcapsule administration. Following the first week of therapy, we observed in all patients a significant decrease in bone pain, improvement in urinary flow obstruction, and a reversal of the signs of prostatism. No side effects were observed, and acceptance of the microcapsules was very good. Our results show that a single dose of D-Trp-6-LH-RH microcapsules suppresses of the pituitary-testicular axis for at least 50 days. D-Trp-6-LH-RH microcapsules facilitate the treatment and should lead to an improvement in the therapeutic response.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Antineoplastic Agents; Capsules; Delayed-Action Preparations; Drug Evaluation; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Luteinizing Hormone; Male; Middle Aged; Pituitary Gland; Prostatic Neoplasms; Testis; Testosterone; Triptorelin Pamoate

Carcinoma of the exocrine pancreas seems to be sex-hormone sensitive. Administration of agonistic analogs of luteinizing hormone--releasing hormone (LH-RH) creates a state of sex-hormone deficiency. Therapy with D-Trp-6-LH-RH was evaluated in 17 patients with unresectable and biopsy-proven adenocarcinoma of the pancreas (stage IV). Nine patients were male and 8 female, and the median age at diagnosis was 60 years. The majority of patients underwent a gastro-intestinal and biliary bypass. The therapy with D-Trp-6-LH-RH was started 3-31 days after bypass surgery. The analog was given at the dose of 1 mg/day subcutaneously for the first 7 days. Subsequently, the dose was reduced to 100 micrograms/day. One month after the start of the therapy the gonadotropin levels were in subnormal range. This therapy led to clinical improvement, better quality of life and an increase in survival time. The median survival time for all the groups was 7.2 months (men 7.4 months and women 6.9 months). LH-RH agonists appear to decrease pancreatic cancer growth by eliminating the stimulatory effect of sex steroids, and by direct effects on tumors. Further improvement in the clinical response in patients with inoperable pancreatic carcinoma might be possibly obtained by the combination of LH--RH agonists with modern somatostatin analogs.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Female; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Pancreatic Neoplasms; Time Factors; Triptorelin Pamoate

Membrane receptors for [D-Trp6]-luteinizing hormone-releasing hormone [( D-Trp6]-LH-RH), somatostatin (SS-14), and epidermal growth factor (EGF) were investigated in experimental N-nitrosobis-(2-oxopropyl)-amine (BOP)-induced pancreatic cancers of hamsters and in specimens of normal human pancreas and human pancreatic cancer obtained from autopsies. Membrane receptors for [D-Trp6]-LH-RH were absent in the pancreas of normal hamsters, but appeared after the carcinoma was induced with BOP. Binding capacity of SS-14 receptors was lower in membranes of BOP-induced pancreatic cancers than in the normal pancreas. In the BOP-induced pancreatic cancers, the receptors were also characterized following in vivo treatment of hamsters with microcapsules of the agonist [D-Trp6]-LH-RH, somatostatin analog RC-160, and the combination of both peptides, which resulted in significant tumor inhibition. Therapy with [D-Trp6]-LH-RH and RC-160, alone or in combination, decreased the binding capacity of receptors for [D-Trp6]-LH-RH, but increased Bmax for SS-14. There were no significant changes in characteristics of the EGF receptor following these therapies. Membranes from human pancreatic cancers showed binding sites for [D-Trp6]-LH-RH, but no binding was detected in normal human pancreas. The presence of receptors for LH-RH in pancreatic tumors of hamster and humans raises the intriguing possibility that LH-RH could be involved in complex interactions that contribute to the appearance of pancreatic cancer. The binding capacity of receptors for SS-14 in human pancreatic cancer membranes was lower, while Bmax for EGF was higher, as compared to normal pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Autopsy; Carcinogens; Cricetinae; ErbB Receptors; Female; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Mesocricetus; Nitrosamines; Pancreatic Neoplasms; Receptors, LHRH; Receptors, Somatotropin; Somatostatin; Triptorelin Pamoate

Membrane receptors for luteinizing hormone-releasing hormone (LH-RH), somatostatin, and prolactin (PRL) were investigated in the Dunning R-3327H rat prostate adenocarcinoma specimens after in vivo treatment with microcapsules of the agonist [D-Trp6]LH-RH and the somatostatin analog RC-160. The LH-RH receptors showed a low-binding affinity (Kd = 54 nM) and high capacity (Bmax = 12.0 pmol/mg). Treatment with the [D-Trp6]LH-RH decreased the binding affinity (Kd = 0.52 microM). Specific somatostatin receptors, with Kd = 1.3 nM and Bmax = 543 fmol/mg, were also found. Treatment with [D-Trp6]LH-RH lowered Bmax to 44 fmol/mg, and administration of RC-160 reduced Kd to 30 nM. After the combined treatment with the two analogs, Kd and Bmax were decreased. Specific PRL receptors (Kd = 0.72 nM; Bmax = 161 fmol/mg) were also detected. Treatment with either analog reduced Bmax by 50%, but a much greater reduction of PRL binding capacity was revealed after in vitro dissociation of the bound endogenous PRL by MgCl2. The dramatic fall in the total number of PRL receptors after combination treatment with both analogs could be partially responsible for the decrease in the weight and volume of prostate tumors. The findings support the concept that analogs of LH-RH and somatostatin can inhibit tumors directly through their own respective receptors. One of several mechanisms of the antineoplastic activity of these analogs could be the elimination of tumor growth-promoting effect of PRL by the reduction of the total number of PRL receptors.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Drug Synergism; Gonadotropin-Releasing Hormone; Male; Prostatic Neoplasms; Rats; Receptors, LHRH; Receptors, Neurotransmitter; Receptors, Prolactin; Receptors, Somatostatin; Somatostatin; Triptorelin Pamoate

Histopathologic changes produced during the treatment of Dunning R3327 prostate cancer with new superactive somatostatin analogs (RC-121 and RC-160) and D-Trp-6 analog of luteinizing hormone-releasing hormone agonist (D-Trp-6-LH-RH) were studied. A significant reduction of the tumor weight could be observed in all treated groups, but the greatest decrease in the tumor volume was seen in the groups receiving the combination of the somatostatin analog and D-Trp-6-LH-RH. Histologically, the treatments resulted in a loss of the tumorous glandular elements and the proliferation of the stromal cells. In the tumors treated with somatostatin analogs, the amount of connective tissue was greatly increased and was accompanied by the appearance of thick collagenous fibers. In the D-Trp-6-LH-RH treated groups, regressive changes in the epithelium were seen in addition to the proliferation of connective tissue. The greatest histologic improvement was observed in the group treated with the combination of RC-160 and D-Trp-6-LH-RH. This histopathologic evaluation clearly supports our contention that superactive analogs of somatostatin greatly potentiate the inhibitory effect of D-Trp-6-LH-RH on the growth of Dunning prostate tumors and may improve the clinical response in patients with prostate cancer.

Topics: Adenocarcinoma; Animals; Antineoplastic Combined Chemotherapy Protocols; Epithelium; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Octreotide; Organ Size; Prolactin; Prostate; Prostatic Neoplasms; Rats; Somatostatin; Testis; Testosterone; Triptorelin Pamoate

The plasma levels of pituitary hormones (LH, FSH and prolactin) as well as testosterone were determined in 62 patients treated with combined therapy using the LHRH agonist [D-Trp6, des-Gly-NH2(10)]LHRH ethylamide and the antiandrogen Flutamide. Plasma radioimmunoassayable LH and FSH levels increased to 534% (p less than 0.01) and 150% (p less than 0.01) of control, respectively, during the first 5 days of treatment, while, afterwards, a marked inhibition was observed which remained constant at approximately 30-50% of control values during the whole period of treatment. All patients showed a decrease of plasma testosterone concentration to approximately 10% of control levels. Detailed determinations of plasma testicular and adrenal steroid levels were then performed in 15 patients. Our data indicate that, except for the blockade of testicular 17-hydroxyprogesterone secretion, the combined therapy has no effect on plasma C-21 steroid levels. However, adrenal C-19 steroids, namely dehydroepiandrosterone and its sulfate, androst-5-ene-3 beta, 17 beta-diol and androstenedione were decreased to approximately 50% of control values (p less than or equal to 0.01). The main testicular steroids, testosterone and dihydrotestosterone, which were increased during the first 10 days of combined administration, rapidly decreased and reached approximately 10% of control values at later time intervals. The present study extends our previous observations indicating that the combined antihormonal treatment affects both testicular and adrenal steroidogenesis. Moreover, we have demonstrated that, up to at least 2 years, this treatment, in addition to decreasing the serum levels of testicular androgens, causes an inhibition of the plasma levels of C-19 steroids from adrenal origin.

Topics: Adenocarcinoma; Adrenal Cortex Hormones; Androgens; Androstane-3,17-diol; Androstenediol; Androstenedione; Androsterone; Anilides; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Dehydroepiandrosterone; Flutamide; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hydrocortisone; Kinetics; Luteinizing Hormone; Male; Pregnenolone; Progesterone; Prolactin; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Sixty-seven previously untreated patients presenting with clinical stage C prostatic carcinoma with no evidence of distant metastases received combination therapy using the antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average duration of treatment of 23.5 months. Only five patients have so far shown treatment failure with 91.8% of the patients still in remission at 2 years. Three patients have died from prostate cancer while three have died from other causes, 93.5% of the patients being alive at 2 years. Local control was achieved rapidly in all except one patient. Urinary obstruction and hydronephrosis were corrected in all cases. When comparing to recent data obtained after single endocrine therapy (orchiectomy or estrogens), or radiotherapy, the rate of treatment failure at 2 years is 3.5-fold lower after combination therapy (8.2%) than monotherapy (28.4%). The death rate at 2 years following start of the combination therapy is 6.5% while it is on average 22.2% (3.4-fold higher) in the studies using monotherapy (orchiectomy or estrogens) or radiotherapy. The present data suggest that treatment of prostate cancer with combination therapy before clinical evidence of dissemination of the disease permits a better response which is possibly explained, at least in part, by the lower degree of dedifferentiation and heterogeneity of the tumors.

Topics: Acid Phosphatase; Adenocarcinoma; Adrenal Cortex Hormones; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Delayed-Action Preparations; Flutamide; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Pancreatic ductal adenocarcinoma was induced in female Syrian golden hamsters by injecting N-nitrosobis(2-oxopropyl)amine (BOP) once a week at a dose of 10 mg per kg of body weight for 18 weeks. Hamsters were then treated with somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) or with [6-D-tryptophan]luteinizing hormone-releasing hormone [( D-Trp6]LH-RH) delayed delivery systems. Microcapsules of somatostatin analog RC-160, designed to release a dose of 5 micrograms/day, were injected twice a month and microcapsules of [D-Trp6]LH-RH, calculated to liberate 25 micrograms per day, once a month. After 18 weeks of BOP administration, the hamsters were divided into three groups of 10-20 animals each. Group I consisted of untreated controls, group II was injected with RC-160, and group III was injected with [D-Trp6]LH-RH. A striking decrease in tumor weight and volume was obtained in animals treated with [D-Trp6]LH-RH or with the somatostatin analog RC-160. After 45 days of treatment with either analog, the survival rate was significantly higher in groups II and III (70%), as compared with the control group (35%). The studies, done by light microscopy, high-resolution microscopy, and electron microscopy, showed a decrease in the total number of cancer cells and changes in the epithelium, connective tissue, and cellular organelles in groups II and III treated with the hypothalamic analogs as compared to controls. These results in female hamsters with induced ductal pancreatic tumors confirm and extend our findings, obtained in male animals with transplanted tumors, that [D-Trp6]LH-RH and somatostatin analogs inhibit the growth of pancreatic cancers.

Topics: Adenocarcinoma; Animals; Cricetinae; Female; Gonadotropin-Releasing Hormone; Mesocricetus; Microscopy, Electron; Mortality; Nitrosamines; Pancreatic Neoplasms; Somatostatin; Triptorelin Pamoate

The combination of a long-acting delivery system for the agonist [D-Trp6]luteinizing hormone-releasing hormone ([D-Trp6]LH-RH) with modern somatostatin analogs was studied in the Dunning R-3327H rat prostate cancer model. Microcapsules of [D-Trp6]LH-RH releasing 25 micrograms/day were injected once a month. In the first experiment the adjunct was the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121), administered at a dose of 2.5 micrograms twice a day, and the therapy was continued for 70 days. Tumor volume was significantly decreased by [D-Trp6]LH-RH microcapsules or RC-121 given alone. The combination of microcapsules and analog RC-121 caused a greater inhibition of tumor growth than the single agents. Similar effects were seen when the percent increase in the tumor volume was examined. The inhibition of tumor growth caused by the [D-Trp6]LH-RH microcapsules was greater than that caused by RC-121. The combination of the two agents was again the most effective, resulting in the smallest increase in tumor volume. Tumor weights were much lower in the groups treated with microcapsules or RC-121 alone than in controls. The lowest tumor weights were obtained in the group that received the combination of [D-Trp6]LH-RH microcapsules and RC-121. Similar results were obtained in the second experiment, in which the animals were treated for a period of 83 days with microcapsules containing the somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) that released 5 micrograms/day and were injected twice a month alone or in combination with microcapsules of [D-Trp6]LH-RH. Microcapsules of analog RC-160 given alone significantly decreased tumor growth as measured by the final tumor volume, the percentage change from the initial tumor volume, and the reduction in tumor weight. The inhibition of tumor growth induced by [D-Trp6]LH-RH microcapsules was greater than that caused by RC-160. The most striking decrease in tumor weight and volume was obtained in animals treated with microcapsules of [D-Trp6]LH-RH combined with the delayed delivery system for RC-160. The overall response to the combination therapy could reflect the inhibition by somatostatin analogs of the proliferation of prostate cancer cells through a decrease in growth hormone and prolactin release and interference with endogenous growth factors, in addition to the main effect, which is the suppression by [D-Trp6]LH-RH of the growth of androgen-dependent tumor cells. Our resu

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Capsules; Drug Compounding; Drug Synergism; Gonadotropin-Releasing Hormone; Male; Octreotide; Organ Size; Prostate; Prostatic Neoplasms; Rats; Somatostatin; Triptorelin Pamoate

Morphological changes produced by the treatment with the D-tryptophan-6 analog of luteinizing hormone-releasing hormone (D-Trp-6-LH-RH) and mitoxantrone (novantrone) were studied in the Dunning R3327H rat prostate cancer model. Microcapsules of D-Trp-6-LH-RH, calculated to release a controlled dose of 25 micrograms/day, were injected intramuscularly once a month. Novantrone (0.25 mg/kg body weight) was injected intravenously once every 3 weeks. The pathology of tumors was studied in two experiments. In the first experiment, the treatment was started 135 days after tumor transplantation, and the therapy was continued for 105 days. In the second experiment, the treatment was initiated 45 days after tumor transplantation, and was carried on for 70 days. The rats were divided into four groups: 1) untreated control, 2) microcapsule-injected, 3) novantrone-injected, and 4) combination of microcapsules and novantrone-injected. In both experiments, similar results were obtained, which included significant reduction in the tumor volume and weight, a very striking decrease in the number of epithelial tumoral cells with atrophy of the glandular epithelium, and an increase in the stromal connective tissue. All these changes were more prominent in the group treated with the combination of microcapsules and novantrone than in the groups treated with microcapsules or novantrone alone. Pathological results support the view that combined therapy may be more efficacious than the treatment with single agents.

Topics: Adenocarcinoma; Animals; Capsules; Gonadotropin-Releasing Hormone; Injections, Intramuscular; Injections, Intravenous; Male; Mitoxantrone; Models, Biological; Prostatic Neoplasms; Rats; Triptorelin Pamoate

Patients (154) with clinical stage D2 prostate cancer with no previous endocrine therapy or chemotherapy received the combination therapy with the pure antiandrogen Flutamide and the LHRH agonist [D-Trp6]LHRH ethylamide for an average of 22 months (3-49 months). The objective response to the treatment was assessed according to the criteria of the US NPCP. There was a 6.3-fold increase (29.2 vs 4.6%) in the percentage of patients who achieved a complete response as compared to the results achieved in five recent studies limited to removal (orchiectomy) or blockade (DES or Leuprolide) of testicular androgens. Only 4.5% of patients did not respond to the combination therapy as compared to an average of 18% by standard therapy. The duration of response is also significantly increased in the patients who received the combination therapy. The death rate was decreased by approximately 2-fold between 2 and 3 yr of treatment. The marked (6.3-fold) improvement in the rate of complete objective responses coupled with the 4-fold decrease in the number of non-responders, the increased duration of the positive responses and the 2-fold decrease in the death rate at 2-3 yr of treatment are obtained with the combination therapy using Flutamide and castration with no or minimal secondary effects.

Topics: Adenocarcinoma; Androgens; Anilides; Combined Modality Therapy; Evaluation Studies as Topic; Flutamide; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Receptors, Androgen; Triptorelin Pamoate

The authors review 55 cases of adenocarcinoma of the prostate, from July 1982 to June 1983. The mean age of these patients was 61.5 years. None of them underwent orchiectomy. They were all treated with an LH-RH analogue: Decapeptyl. In 74.5% of the patients a consistent decrease of tumour mass in the prostate to about half its original size was observed, in association with a shrinking of the metastases. The Karnofsky index improved in 89% of the patients. The authors believe that Decapeptyl is preferable to surgical castration because it allows an improvement in pain symptoms, a regression of the primary tumour and metastases and achieves a better balance of serum levels of testosterone, FSH and LH.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents; Drug Evaluation; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Time Factors; Triptorelin Pamoate

Topics: Adenocarcinoma; Adult; Aged; Female; Gonadotropin-Releasing Hormone; Humans; Male; Pancreatic Neoplasms; Triptorelin Pamoate

Topics: Acute Kidney Injury; Adenocarcinoma; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostatic Neoplasms; Triptorelin Pamoate

Since the first observation reported by Huggins et al. in 1941, hormonal treatment of advanced prostatic cancer has been directed primarily at neutralizing testicular androgens by orchiectomy or estrogen therapy. These two approaches yielded a 60 to 80% positive response rate in the many studies carried out over the last forty years. However, responses were short-lived and the disease recurred rapidly in nearly every case. A possible reason for these limited results may well be related to the fact that a unique characteristic of man as compared to other species is a high level of secretion of adrenal steroids that act as precursors and are converted into androgens within the prostatic tissue itself. Complete neutralization of both testicular and adrenal androgens is therefore mandatory to achieve total suppression of the influence of androgens on the carcinoma. To accomplish this goal, we have used a combination of an LHRH agonist (or orchiectomy) and a pure antiandrogen in fifty-two previously untreated patients with prostatic carcinoma and bone metastases (stage D2). Average duration of treatment was eighteen months (six to thirty-two months). An objective positive response assessed according to the criteria set forward by the National Prostatic Cancer Project (NPCP) was recorded during the first treatment months in every case, a significant improvement over the 60 to 80% positive response rate following previous treatments confined to neutralization of testicular androgens by orchiectomy or estrogens.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Imidazoles; Imidazolidines; Male; Middle Aged; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Triptorelin Pamoate

Chronic treatment of adult men with LHRH agonists causes a decrease in serum testosterone and 5 alpha-dihydrotestosterone to castrate levels. In the presence of such low levels of circulating testicular androgens, the concentration of serum LH measured by radioimmunoassay (RIA) sometimes remains normal or is only partially inhibited. In order to assess the biological activity of circulating LH, we have used the mouse interstitial cell assay. Blood samples were obtained from patients with prostatic carcinoma treated with the LHRH agonist [D-Trp6] LHRH ethylamide in combination with the pure antiandrogen Flutamide (Euflex). While serum LH levels measured by RIA were only partially reduced from 2.2 +/- 0.3 (SEM) to 1.1 +/- 0.1 ng/ml after 3 months of therapy, bioactive LH was markedly inhibited from 0.43 +/- 0.04 to 0.030 +/- 0.007 ng/ml, thus causing the ratio of biologically active to radioimmunoassayable LH to drop from 0.26 +/- 0.03 to 0.03 +/- 0.01. In the same patients, serum testosterone levels were decreased from 3.91 +/- 0.51 to 0.14 +/- 0.05 ng/ml after 3 months of treatment. In patients treated for 6 months, the bio/immuno ratio was still reduced at 0.032 +/- 0.005. These data show a marked loss of LH biological activity during treatment of adult men with an LHRH agonist and an antiandrogen. The close parallelism observed between serum testosterone and bioactive LH levels suggests that the loss of biological activity of the gonadotrophin is mainly, if not exclusively, responsible for the inhibition of testicular androgen secretion observed during chronic treatment with LHRH agonists.

Topics: Adenocarcinoma; Anilides; Animals; Biological Assay; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Mice; Prostatic Neoplasms; Radioimmunoassay; Testosterone; Triptorelin Pamoate

Twenty-five patients with prostatic carcinoma were involved in a Gehan's oriented phase II trial of D-Trp6-LH-RH in daily doses of 500 mcg for 7 days and 100 mcg for 3 months, this lapse of time being considered optimal for evaluation of the short-term response to treatment in this disease. Serum levels of LH and testosterone decreased rapidly. After 3 months of treatment, pain had disappeared in 14/21 patients; urinary symptoms had completely regressed in 10/22 patients and partially regressed in 9. A more than 50% reduction in prostatic enlargement was detected by ultrasonography in 7/19 patients, and the overall proportion of regression at scintigraphy was 43%. Prostatic acid phosphatases decreased by more than 50% in 10/15 patients. The results obtained with this LH-RH agonist were equivalent to those of orchidectomy and oestrogen therapy. The new drug was well tolerated. Although some of the patients treated are still responding after more than 15 months of treatment, further studies are required to evaluate the duration of response.

Topics: Adenocarcinoma; Aged; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Male; Prostatic Neoplasms; Time Factors; Triptorelin Pamoate

Topics: Adenocarcinoma; Aged; Brachytherapy; Cesium Radioisotopes; Cyproterone; Cyproterone Acetate; Estrogens; Gonadotropin-Releasing Hormone; Humans; Iridium; Lymph Node Excision; Male; Middle Aged; Orchiectomy; Prostatectomy; Prostatic Neoplasms; Triptorelin Pamoate

Experiments were undertaken with estrogen-dependent mammary carcinomas in rats and mice to determine the antitumor activities of agonistic and antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH). Chronic administration of the agonist [D-Trp6]LH-RH or of antagonist 1 ( [NAc-D-p-Cl-Phe1,2-Phe3,D-Arg6-D-Ala10]LH-RH) at doses of 25 and 50 micrograms/day, respectively, for 21 days to mice bearing the MXT mammary carcinoma significantly decreased tumor weight and volume. The weight of the ovaries and serum progesterone levels in mice treated with [D-Trp6]LH-RH or antagonist 1 were also significantly reduced. In rats bearing the MT/W9A mammary adenocarcinoma, chronic administration of [D-Trp6]LH-RH at a dose of 25 micrograms twice a day or of antagonist 2 ( [NAc-D-p-Cl-Phe1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH) at a dose of 50 micrograms twice a day for 28 days significantly decreased tumor weight and volume. Chronic treatment with either [D-Trp6]LH-RH or antagonist 2 markedly diminished the weight of the ovaries and serum levels of both estrogen and progesterone. Serum luteinizing hormone was significantly decreased in rats treated with antagonist 2 but not in rats treated with [D-Trp6]LH-RH. There was a significant drop in serum prolactin levels in rats treated with [D-Trp6]LH-RH but not in those receiving antagonist 2. Regression of mammary tumors in rats and mice in response to chronic administration of [D-Trp6]LH-RH and the two antagonistic analogs of LH-RH suggests that these compounds should be considered for the development of a new hormone therapy for breast cancer in women.

Topics: Adenocarcinoma; Animals; Cell Division; Estradiol; Gonadotropin-Releasing Hormone; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Progesterone; Rats; Rats, Inbred Strains; Triptorelin Pamoate