trelstar and Carcinoma

Topics: Age Factors; Carcinoma; Clinical Trials as Topic; Disease Models, Animal; Female; Follicle Stimulating Hormone; Gonadotropins; Goserelin; Humans; Leuprolide; Luteinizing Hormone; Menopause; Middle Aged; Ovarian Neoplasms; Receptors, LHRH; Remission Induction; Risk Factors; Survival Rate; Treatment Outcome; Triptorelin Pamoate

Between March and September 1988, 74 patients with progressive ovarian cancer after prior platinum-based therapy were treated with the luteinizing hormone-releasing hormone (LHRH) agonist Triptorelin (Decapeptyl degrees). Treatment consisted of i.m. injection of 3.75 mg of microencapsulated Triptorelin on days 1, 8 and 28 followed by 4-weekly injections until tumor progression. No objective responses were observed. Eleven out of 68 evaluable patients (16%) had stable disease. The median progression-free survival was 5 months in patients with disease stabilization and 2 months for all evaluable patients. The median survival for patients with disease stabilization was 17 months, whereas for all patients it was 4 months. The treatment was well tolerated; the only reported adverse events were incidental hot flushes. This study showed that the LHRH agonist Triptorelin has only modest efficacy in patients pretreated with platinum-containing chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Carcinoma; Drug Evaluation; Drug Resistance; Female; Humans; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Platinum Compounds; Salvage Therapy; Survival Rate; Treatment Outcome; Triptorelin Pamoate

Several lines of evidence suggest that the proliferation of ovarian carcinoma might be stimulated by gonadotrophins. A number of Phase I/Phase II clinical trials have reported that the suppression of endogenous luteinizing hormone and follicle-stimulating hormone secretion by luteinizing hormone-releasing hormone (LHRH) analogs induced objective remissions and/or disease stabilization in 10-30% of patients with advanced refractory ovarian carcinoma. The current study was performed to evaluate whether the addition of LHRH agonist treatment to standard platinum-based chemotherapy could prolong survival of patients with surgically treated Stage III or IV epithelial ovarian carcinoma.. One hundred and thirty-five patients with Stage III or IV epithelial ovarian carcinoma participated in this prospective randomized double blind trial. After cytoreductive surgery, 69 patients received monthly injections of a depot preparation of the LHRH agonist [D-Trp6] LHRH (triptorelin, 3.75 mg) and 66 patients received placebo until their deaths or termination of trial, respectively. All patients were treated with a standard platinum-based chemotherapy, and, if necessary, with second- or third-line cytotoxic regimens.. Endogenous gonadotrophins were reliably suppressed in patients treated with triptorelin. However, their progression free and overall survival were not significantly different from that of patients receiving placebo injections (statistical power > 80% for a difference between both groups of > or = 20%).. The results of this trial suggest that the suppression of endogenous gonadotrophins by conventional doses of an LHRH agonist produces no relevant beneficial effects in patients with advanced ovarian carcinoma who receive standard surgical cytoreduction and cytotoxic chemotherapy.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Double-Blind Method; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Middle Aged; Ovarian Neoplasms; Prospective Studies; Survival Analysis; Triptorelin Pamoate

Fourteen patients with advanced ovarian cancer who failed chemotherapy received a long-acting LHRH agonist. All the patients had been previously operated on and all had received at least one regimen of chemotherapy. Duration of decapeptyl administration was between 1 month and 28 weeks. There were no complete or partial responses. Eight patients (57%) had disease stabilization with a median progression-free interval of 14 weeks (range 4-28 weeks). All other patients developed a clear progressive cancer after the first injection of LHRH agonist. Three of these patients are still alive and receiving other forms of chemotherapy (median follow-up after the end of LHRH treatment was 11.5 months). The regimen was well tolerated with only mild toxicity observed (hot flushes in 2 patients). Although D-Trp-6-LHRH (Decapeptyl) was well tolerated, it had insignificant activity in treating patients with epithelial cancer that was resistant or relapsed after first-line platinum-based chemotherapy.

Topics: Aged; Carcinoma; Female; Humans; Injections, Intramuscular; Middle Aged; Ovarian Neoplasms; Salvage Therapy; Treatment Failure; Triptorelin Pamoate

Ninety-five patients with stage C (C1 + C2) or D (D1 + D2) prostatic carcinoma were treated with the depot formulation of D-TRP-6 LH-RH ("Decapeptyl") for up to 33 months. Serum testosterone (T) levels were significantly reduced to castration levels within 4 weeks and maintained persistently low. Similarly, LH levels were decreased, although they remained in the normal range. Stimulation tests with either Gn-RH or HCG in course of treatment showed the achievement of a complete pituitary desensitization and almost a complete down-regulation of testicular LH receptors. Of 88 patients evaluable for response, about one-half showed an objective response. In most cases, subjective improvement with relief of bone pain and/or urinary symptoms was obtained without major side effects. These results indicate that the depot formulation of D-TRP-6 LH-RH offers an effective therapeutic alternative for patients with advanced prostatic cancer.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma; Clinical Trials as Topic; Delayed-Action Preparations; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Gonadotropin‑releasing hormone (GnRH), or its analogues have been demonstrated to exhibit anti‑proliferative effects on tumour cells in ovarian, endometrial and breast cancer through GnRH‑receptors (GnRH‑R). However, the role of GnRH in nasopharyngeal carcinoma (NPC) remains to be elucidated. In order to investigate the effects of GnRH in NPC, the present study examined the expression of the GnRH‑R transcript in NPC and investigated the phenotypic changes in HK1 cells, a recurrent NPC‑derived cell line, upon receiving GnRH treatment. Firstly, the GnRH‑R transcript was demonstrated in the NPC cell lines and four snap frozen biopsies using reverse transcription‑quantitative polymerase chain reaction. In addition, immunohistochemistry revealed the expression of GnRH‑R in two of the eight (25%) NPC specimens. Treatment with GnRH induced a rapid increase in intracellular ionised calcium concentration in the NPC cells. GnRH and its agonists, triptorelin and leuprolide, exerted anti‑proliferative effects on the NPC cells, as determined using an MTS assay. GnRH did not induce any cell cycle arrest in the HK1 cells under the conditions assessed in the present study. Time‑lapse imaging demonstrated a reduction in cell motility in the GnRH‑treated cells. In conclusion, GnRH, or its analogues may have antitumour effects on NPC cells. The consequences of alterations in the levels of GnRH on the progression of NPC require further examination.

Topics: Antineoplastic Agents, Hormonal; Carcinoma; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gonadotropin-Releasing Hormone; Humans; Immunohistochemistry; Leuprolide; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Receptors, LHRH; Triptorelin Pamoate

The effects of the gonadotropin releasing hormone (GnRH) agonist (D-Trp(6)) were examined in two human ovarian cancer cell lines and in severe combined immune deficiency (SCID) mice to evaluate its potential as a cytocidal, cytostatic, or differentiating antitumor agent.. We treated the human ovarian cancer cell lines OVCAR-3 and SKOV-3 for 5 or 7 days and sex-matched SCID mice with GnRH agonist for 29 days. The antitumor effect of GnRH agonist were studied in various aspects. To confirm the antiproliferative effect, we used 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide colorimetric assay, in vitro, and a serial measurement of tumor growth in vivo. The disturbances of progression in the cell cycle and the changes of cyclin-dependent kinase 1 following treatment with GnRH agonist were evaluated with flow cytometric analysis in vitro. The induction of apoptosis following treatment with GnRH agonist was studied using in situ terminal deoxyribonucleotidyl transferase (Tdt) and further quantitated with ELISA in vitro. The presence of telomerase activity following treatment with GnRH agonist was measured by PCR-based telomeric repeat amplification protocol and ELISA detection in cell lines and xenografts in vitro and in vivo.. Continuous exposure of cell lines and xenografts to GnRH agonist resulted in growth inhibition of cancer cells in a dose- and time-dependent manner. In cultured cells, the GnRH agonist blocked cell cycle progression in G0/G1 phase and thus reduced the number of cells in S and G2/M phases. The phenomenon of apoptosis was documented in cultured cells treated with GnRH agonist by in situ Tdt assay. The frequency of apoptotic cells in the in situ Tdt assay was 5-6% compared with control, 4-5%. Apoptosis quantified by ELISA revealed a high incidence in cultured cells treated with GnRH agonist. The activities of telomerase in cell lines and xenografts were not decreased by GnRH agonist. There were not any significant changes of expression of CA-125 by flow cytometry and of the cellular morphology observed with light microscopy.. Our results indicate that the antiproliferative effect of GnRH agonist in epithelial ovarian cancer cells may be mainly attributed to cytostatic activities resulting in blocking of cell cycle progression in the G0/G1 phase and minimally related to the induction of apoptosis.

Topics: Animals; Antineoplastic Agents, Hormonal; Apoptosis; Carcinoma; CDC2 Protein Kinase; Cell Cycle; Cell Differentiation; Female; Mice; Mice, SCID; Ovarian Neoplasms; Triptorelin Pamoate; Tumor Cells, Cultured

The experience from using different hormonal trials in 33 ovarian cancer patients, who were beyond the stage of standard therapies and experimental cytotoxic therapies in a single institution, are reported. Agents used were progestins, an antiestrogen (tamoxifen), an antiandrogen (flutamide) and a GnRH-agonist (decapeptyl). Twenty-one patients completed at least 8 weeks of treatment. Two patients obtained an objective response (10%): one partial response on tamoxifen for 6 months and one complete response on decapeptyl for 38 + months. Two further patients achieved disease stabilizations on tamoxifen and flutamide for 6 and 8 months respectively. Although the objective response rate with hormonal therapies is limited in these circumstances the absence of important toxicities favor their use. It is suggested to further study this in patients who do not reach a complete response after standard induction chemotherapy, particularly in those with well-differentiated tumors.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Carcinoma; Estrogen Antagonists; Female; Flutamide; Gonadotropin-Releasing Hormone; Humans; Luteolytic Agents; Medroxyprogesterone Acetate; Megestrol; Megestrol Acetate; Middle Aged; Ovarian Neoplasms; Progesterone Congeners; Remission Induction; Survival Rate; Tamoxifen; Triptorelin Pamoate

A series of 115 previously untreated patients displaying clinical stage C prostatic carcinoma with no evidence of distant metastases received combination therapy using the antiandrogen flutamide and the LHRH agonist [D-Trp6, des-Gly-NH(2)10]LHRH ethylamide; the average follow-up was 3.9 years. Twenty-eight patients showed treatment failure with a probability of disease-free survival of 91.2% at 2 years. Twenty patients died from prostate cancer and 10 from other causes, the survival probability being 93.4% at 2 years. Local control was achieved rapidly in all patients. Urinary obstruction and hydronephrosis were corrected in all cases. When compared with data obtained after single endocrine therapy (orchiectomy or oestrogens) or radiotherapy, the treatment failure rate at 2 years was more than 3.0-fold lower after combination therapy (8.8%) than monotherapy (28.4%). The death rate 2 years after the start of combination therapy was 6.6% and was on average 22.2% (3.6-fold higher) in the studies using monotherapy (orchiectomy or oestrogens) or radiotherapy. The present data suggest that treatment of prostate cancer with combination therapy before clinical evidence of dissemination of disease permits more efficient control of local disease and a decreased rate of progression to metastatic disease.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Carcinoma; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostatic Neoplasms; Survival Rate; Triptorelin Pamoate

We have been interested in the possible direct effects of luteinizing hormone releasing hormone (LHRH) and somatostatin (SS) analogs on the growth of human mammary tumor cells. Four recently synthesized peptide hormones including the LHRH agonists D-Trp6-LHRH and zoladex, LHRH antagonists SB30 and SB75, and the somatostatin analog RC 160 were analyzed for their effects on DNA synthesis of MCF-7 breast cancer cells in culture. At 48 hr, D-Trp6-LHRH and SB30 did not show significant effects (dose range, 10(-12)-10(-6) M). However, the combination of these two peptides at 10(-10) M produced significant inhibition of 3[H]thymidine incorporation (50% control). At 72 hr in the absence of estradiol-stimulated growth, D-Trp6-LHRH showed inhibition at 10(-12) and 10(-10) M (P less than 0.005 and 0.001). At higher concentrations, no significant inhibition was noted. In contrast to D-Trp6, SB30 (antagonist) showed no inhibition but significant stimulation of DNA synthesis at 10(-6) and 10(-4) M. In the presence of added estradiol (10(-9) M), complete reversal of D-Trp6-LHRH analog inhibition is noted. In contrast, there is persistent stimulation by SB30 (P less than 0.001). At 96 hr, D-Trp6-LHRH continued to show maximal inhibition of 70% in the absence of estradiol. SB30 stimulated DNA synthesis 100% at 10(-6) M. At 72 hr, the SS analog RC 160 demonstrated significant inhibition (53%) that was similar to D-Trp6 and SB75 peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Agents; Breast Neoplasms; Buserelin; Carcinoma; Cell Division; Estrogens; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; In Vitro Techniques; Somatostatin; Triptorelin Pamoate; Tumor Cells, Cultured

Twenty-two patients with locally advanced prostatic carcinoma stage T3, N0, M0 have been treated with LH-RH agonists during a mean time of 5 months prior to radical retropubic prostatectomy. Although tumors appeared to be confined to the organ in 68% of the patients after endocrine treatment, pathological examination of the surgical specimens showed in 89% evidence of extraprostatic disease, which questions the clinical impression of 'downstaging'. A disparity between the tumor grade of the biopsy and that of the operative specimen as well as an increased size of tumor-involved lymph nodes despite endocrine treatment led us to speculate that a certain proportion of patients will bear the risk of disease progression during preoperative androgen deprivation. Furthermore, there was local recurrence early in the postoperative course and at the high rate of 39%.

Topics: Aged; Biopsy; Carcinoma; Combined Modality Therapy; Cyproterone Acetate; Humans; Male; Neoplasm Recurrence, Local; Prostate; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Time Factors; Triptorelin Pamoate

Topics: Antineoplastic Agents; Buserelin; Carcinoma; Gonadotropin-Releasing Hormone; Humans; Male; Neoplasm Recurrence, Local; Orchiectomy; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

The hormonal effects of a delayed-release intramuscular (IM) preparation of D-Trp-6-LH-RH (TRP-6 microcapsules) were investigated in men aged 65-75 years. Six men with a prostatic adenoma (group A) received subcutaneously (SC) 500 micrograms TRP-6/day from day 0 to day 6. Seven men with a prostatic carcinoma (group B) were given the same SC treatment, but in addition received on days 7, 28 and 56 an intramuscular injection of 3 mg TRP-6 microcapsules. During SC treatment, plasma TRP-6 levels rose to 2-4 ng/ml. Plasma LH peaked on day 1, whereas high testosterone levels were maintained from day 2 to day 4, and then fell abruptly on day 6. In five subjects from group B, plasma TRP-6 was detectable in all plasma samples from day 10 to day 49. Testosterone levels were in the castrate range after day 24. Mean LH level decreased progressively from day 14 to day 56. These data provide evidence for the efficacy of periodic administration of TRP-6 microcapsules for suppressing testicular secretion.

Topics: Aged; Capsules; Carcinoma; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Injections, Subcutaneous; Luteinizing Hormone; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

To ascertain whether the immunoreactive luteinizing hormone (LH) levels measured following the combined treatment may represent cross-reaction of the LH antiserum with LH subunits, we have examined the effects of therapy on the serum levels of free alpha- and free LH-beta-subunits in intact, castrated, and estrogen-treated patients. In previously untreated patients receiving the LHRH agonist [D-Trp6,des-Gly-NH2(10)]LHRH ethylamide in association with the pure antiandrogen Flutamide, serum-free alpha-subunit levels were stimulated from 0.09 +/- 0.02 to 3.10 +/- 0.84 ng/ml after 5 days, and declined slowly afterwards to 1.33 +/- 0.20 ng/ml after 3 months of combined treatment. In patients pretreated from 12 to 24 months (17.5 +/- 1.0 months) with diethylstilbestrol (DES) prior to receiving the combined therapy, free serum alpha-subunit concentration followed a similar pattern, rising from 0.22 +/- 0.03 to 1.78 +/- 0.28 ng/ml after 15 days of combined treatment, and declining thereafter to 0.81 +/- 0.10 ng/ml after 3 months. Free LH-beta-subunits were below the detection limit in most previously untreated patients and in all DES-treated patients. After correcting for the cross-reactivity of the alpha-subunit in the LH RIA, immunoassayable LH serum levels in previously untreated patients were only slightly reduced from 0.81 +/- 0.06 ng/ml before the onset of the combined treatment to 0.52 +/- 0.05 ng/ml after 3 months. On the contrary, bioactive serum LH levels were drastically inhibited from 0.43 +/- 0.04 to 0.03 +/- 0.01 ng/ml after the same duration of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Androgen Antagonists; Anilides; Carcinoma; Castration; Flutamide; Glycoprotein Hormones, alpha Subunit; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Osmolar Concentration; Peptide Fragments; Pituitary Hormones, Anterior; Prostatic Neoplasms; Stimulation, Chemical; Triptorelin Pamoate

Various approaches to hormonal treatment of prostate carcinoma are discussed. Eighty-one patients with prostatic carcinoma, eight with stage B, nine with stage C, and 64 with stage D disease, were treated subcutaneously daily for 3 months with the LH-RH agonist D-Trp-6-LH-RH (Decapeptyl) in order to evaluate the incidence of remissions according to WHO recommendations for oncologic trials. The findings were compared to those obtained with other hormonal therapies of prostatic carcinoma according to the statistical method of "expected response rate" as adapted by Lee and Wesley for phase II trials. Treatment with D-Trp-6-LH-RH greatly reduced serum LH and testosterone levels without raising serum prolactin. After 1-2 weeks of therapy, there was relief of subjective symptoms and a reversal of the signs of prostatism as well as a marked decrease in bone pain. At 90 days 52 patients had complete relief of prostatism and 21 had only mild signs and symptoms. Seventy patients were experiencing no bone pain and an additional six had only mild pain. Prostatic size, evaluated by rectal examination and transabdominal ultrasonography, reverted to normal in 26.4% of patients (complete remission) and was reduced by more than 50% in an additional 17.6% (partial remission), the overall rate of complete plus partial regression of prostatic enlargement being 44%. Scans showed a major improvement of bone lesions in 14.8% of cases. This response increased to 37% after more than 6 months of follow-up. Prostatic acid phosphatase levels were decreased by more than 50% in 61% of the patients, but this test appears to be a less valid marker than the lipid-associated sialic acid (LASA). The increase in LASA before treatment and a reduction after treatment can frequently be correlated with the objective volume of the neoplasms. No flare-up of the disease was encountered, and there were no side effects except for impotence. Statistical analyses of results by the method of Lee and Wesley indicated that the incidence of complete and partial regression (CR and PR) observed with D-Trp-6-LH-RH was not significantly different from that recorded in previous studies for another LH-RH analog, Buserelin. However, CR and PR obtained with D-Trp-6-LH-RH (44%) were significantly higher than with subcapsular orchiectomy (22%). Hormonal effects and some other actions of D-Trp-6-LH-RH were compared and contrasted with those produced by castration, estrogens, antiandrogens, and progestogens.(ABSTRACT

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Carcinoma; Drug Administration Schedule; Drug Evaluation; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate

Topics: Androgen Antagonists; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Carcinoma; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Triptorelin Pamoate

Ten patients with prostatic carcinoma--six with stage C and four with stage D disease--were treated for 6 weeks to 12 months with agonistic analogues of luteinizing hormone-releasing hormone (LH-RH). [D-Trp6]LH-RH was given subcutaneously once daily at a dose of 100 microgram and [D-Ser(But)6]des-GlyNH2(10)-LH-RH ethylamide (HOE 766) was given subcutaneously (50 microgram once daily) or intranasally (500 microgram twice daily). In all patients, mean plasma testosterone levels showed a 75% suppression by the third week of treatment and remained low thereafter. This was followed by a decrease or normalization of plasma acid phosphatase levels by the second month of treatment and a 47% decrease in serum alkaline phosphatase by the 10th week of treatment in all but one patient. In patients with stage C disease presenting with prostatism or urinary outflow obstruction, there was a noticeable clinical improvement. In two such patients, a decrease in the size of the prostate was confirmed by ultrasonography. In patients with stage D disease manifested by diffuse bone metastases, there was relief of bone pain, and in one patient treated for greater than 12 months the improvement was documented by radioisotope bone imaging. It is concluded that superactive agonistic LH-RH analogues hold promise as therapeutic agents in patients with androgen-sensitive prostatic adenocarcinoma. Furthermore, the analogous of LH-RH may be used to assess the responsiveness of patients to surgical castration. Long-term administration of LH-RH analogues could become an alternative to surgical castration and estrogen therapy for the treatment of hormone-dependent prostatic carcinoma.

Topics: Buserelin; Carcinoma; Estradiol; Gonadotropin-Releasing Hormone; Humans; Male; Prostatic Neoplasms; Testosterone; Triptorelin Pamoate