trelstar and Lung-Neoplasms

To report the outcome and course of disease in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel followed by abiraterone acetate in a single center.. In this retrospective observational study, we reviewed the course of disease of all applicable patients with mCRPC treated with docetaxel followed by abiraterone at our center. We analyzed progression-free survival (PFS) of docetaxel and abiraterone treatments. We further searched for predictive factors for the duration of treatment response.. Median PFS between initiation of androgen deprivation therapy and the diagnosis of mCRPC was 32 months. Median PFS on docetaxel treatment was 9 months. Median PFS on abiraterone treatment was 11 months. Patients with higher Gleason scores (GS) (8-10) at initial diagnosis had a significantly longer median PFS on docetaxel as compared to patients with GS 6-7, p = 0.01. We demonstrate a significant correlation between the PFS on docetaxel and PFS on abiraterone in the post-docetaxel setting (Kendall tau r = 0.32, p = 0.019) as well as a significant negative correlation between the PSA nadir under abiraterone treatment and the time to progression under abiraterone (Kendall tau r = -0.43, p = 0.007).. High Gleason score appears to be predictive of duration of response to docetaxel. Interestingly, progression-free survival with abiraterone appears to be correlated with the duration of response with docetaxel, whereas PSA decline and low nadir appear to be predictive of response to abiraterone.

Topics: Aged; Androgen Antagonists; Androstenes; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Cohort Studies; Disease-Free Survival; Docetaxel; Flutamide; Humans; Leuprolide; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Nitriles; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Taxoids; Tosyl Compounds; Treatment Outcome; 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

To evaluate the efficacy of a novel docetaxel derivative of deslorelin, a luteinizing hormone-releasing hormone (LHRH) agonist, and its combination in vivo with RGD peptide conjugated nanoparticles encapsulating an antiangiogenic, anti-vascular endothelial growth factor (VEGF) intraceptor (Flt23k; RGD-Flt23k-NP) in H1299 lung cancer cells and/or xenografts in athymic nude BALB/c mice.. The in vitro and in vivo efficacy of the deslorelin-docetaxel conjugate was evaluated in H1299 cells and xenografts in athymic nude mice. Coadministration of deslorelin-docetaxel conjugate and RGD-Flt23k-NP was tested in vivo in mice. Tumor inhibition, apoptosis, and VEGF inhibition were estimated in each of the treatment groups.. The conjugate enhanced in vitro docetaxel efficacy by 13-fold in H1299 cells compared with docetaxel at 24 hours, and this effect was inhibited following reduction of LHRH receptor expression by an antisense oligonucleotide. Combination of the conjugate with the RGD-Flt23k-NP in vivo resulted in an 82- and 15-fold tumor growth inhibition on day 39 following repeated weekly i.v. injections and a single intratumoral (i.t.) injection, respectively. These effects were significantly greater than individual targeted therapies or docetaxel alone. Similarly, apoptotic indices for the combination therapy were 14% and 10% in the i.v. and i.t. groups, respectively, and higher than the individual therapies. Combination therapy groups exhibited greater VEGF inhibition in both the i.v. and i.t. groups.. Docetaxel efficacy was enhanced by LHRH receptor-targeted deslorelin conjugate and further improved by combination with targeted antiangiogenic nanoparticle gene therapy. Combination of novel targeted therapeutic approaches described here provides an attractive alternative to the current treatment options for lung cancer therapy.

Topics: Animals; Cell Line, Tumor; Drug Delivery Systems; Gene Transfer Techniques; Humans; Lung Neoplasms; Medical Oncology; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Oligonucleotides, Antisense; Oligopeptides; Triptorelin Pamoate; Vascular Endothelial Growth Factor A

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

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

Analogues of somatostatin (SS) and luteinizing hormone-releasing hormone (LH-RH) activate tyrosine phosphatases in MIA PaCa-2 human pancreatic cancer cell line membranes and inhibit growth. We compared the substrates phosphorylated by epidermal growth factor (EGF) to those dephosphorylated by the SS analogue RC-160 (D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2) and [D-Trp6]LH-RH in cancer cell lines such as MIA PaCa-2 (human pancreatic cancer), HCPC (hamster cheek pouch carcinoma), A-549 (human lung cancer), HT-29 (human colon cancer), and R3230AC (breast cancer). EGF phosphorylated proteins of 170, 65, and 60 kDa and analogues of SS and LH-RH promoted the dephosphorylation of these proteins in MIA PaCa-2 and HCPC cell lines. The EGF receptor is 170 kDa. pp60src (60 kDa) is known to be a substrate for EGF receptor. The LH-RH receptor is also 60 kDa. The effects of RC-160 and [D-Trp6]LH-RH were quantitatively different. Examinations of HT-29, A-549, and R3230AC cancer cell lines revealed no phosphorylation by EGF or dephosphorylation by RC-160 and [D-Trp6]LH-RH. In addition to the 170-, 65-, and 60-kDa proteins, 35-kDa proteins were also phosphorylated in some cancer cell lines. This work demonstrates that analogues of SS and LH-RH can reverse the effects of EGF biochemically as well as functionally.

Topics: Amino Acid Sequence; Animals; Antineoplastic Agents; Autoradiography; Breast Neoplasms; Cell Line; Colonic Neoplasms; Epidermal Growth Factor; Gonadotropin-Releasing Hormone; Humans; Kinetics; Lung Neoplasms; Membrane Proteins; Molecular Sequence Data; Pancreatic Neoplasms; Phosphorus Radioisotopes; Phosphorylation; Protein Kinases; Protein-Tyrosine Kinases; Somatostatin; Triptorelin Pamoate; Tyrosine

The lung is an infrequent location of extragenital endometriosis, an exceptional cause of hemoptysis or pneumothorax. Adequate management has not yet been well established. We present two cases of pulmonary endometriosis, parenchymal and pleural. The presenting symptoms were catamenial hemoptysis and pneumothorax, respectively, which were treated with GnRH analogues. The first patient received Buserelin (900 micrograms/day intranasally) for 6 months. After 15 months of normal menstrual activity, the symptoms reappeared. The patient was then treated with Triptorelin (3.75 mg/month intramuscularly) for 6 months and remains asymptomatic and menstruating 14 months after discontinuing treatment. The patient presenting with pneumothorax was treated with leuprolide (1 mg/day subcutaneously) for 6 months and is asymptomatic 1 year after stopping treatment. These results suggest that GnRH analogues may be an acceptable alternative to danazol in the medical management of pulmonary endometriosis.

Topics: Administration, Intranasal; Adult; Antineoplastic Agents; Buserelin; Endometriosis; Female; Gonadotropin-Releasing Hormone; Hemoptysis; Hormones; Humans; Leuprolide; Lung Neoplasms; Pneumothorax; Triptorelin Pamoate

Pulmonary endometriosis has been described as occurring in two forms: --bronchopulmonary with haemoptysis at the periods, --pleuropulmonary with pneumothorax at the periods. In 30-40% of cases it is associated with pelvic endometriosis. The pathways along which it can be disseminated are: --transdiaphragmatic peritoneal migration, --or metastatic migration through the veins and lymphatics. The treatment at present consists of hormone therapy together with surgery.

Topics: Adult; Chest Tubes; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Lung Neoplasms; Luteolytic Agents; Menstruation; Pneumothorax; Recurrence; Thoracostomy; Triptorelin Pamoate

Topics: Diagnosis, Differential; Gonadotropin-Releasing Hormone; Humans; Lung; Lung Neoplasms; Male; Middle Aged; Pneumoconiosis; Prostatic Neoplasms; Triptorelin Pamoate

Topics: Aged; Gonadotropin-Releasing Hormone; Humans; Lung Neoplasms; Male; Prostatic Neoplasms; Triptorelin Pamoate