goserelin and abiraterone

The combined use of androgen deprivation therapy (ADT) and image-guided radiotherapy (IGRT) can improve overall survival in aggressive, localized prostate cancer. However, owing to the adverse effects of prolonged ADT, it is imperative to identify the patients who would benefit from this combined-modality therapy relative to the use of IGRT alone. Opportunities exist for more personalized approaches in treating aggressive, locally advanced prostate cancer. Biomarkers--such as disseminated tumour cells, circulating tumour cells, genomic signatures and molecular imaging techniques--could identify the patients who are at greatest risk for systemic metastases and who would benefit from the addition of systemic ADT. By contrast, when biomarkers of systemic disease are not present, treatment could proceed using local IGRT alone. The choice of drug, treatment duration and timing of ADT relative to IGRT could be predicated on these personalized approaches to prostate cancer medicine. These novel treatment intensification and reduction strategies could result in improved prostate-cancer-specific survival and overall survival, without incurring the added expense of metabolic syndrome and other adverse effects of ADT in all patients.

Topics: Androgen Antagonists; Androstenes; Benzamides; Biomarkers; Combined Modality Therapy; Dose-Response Relationship, Radiation; Flutamide; Goserelin; Humans; Male; Neoplasm Recurrence, Local; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms; Radiotherapy, Image-Guided; Risk Assessment; Treatment Outcome

Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression.. A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry.. A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse.. Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression. Preliminary analysis of the clinical data is also promising, with excellent PSA nadir and no relapse to date in this high-risk population.

Topics: Androgen Antagonists; Androgens; Androstenes; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Neoadjuvant Therapy; Prednisone; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Time Factors

Topics: Aged, 80 and over; Androstenes; Anilides; Antibodies, Monoclonal, Humanized; Antigens, Surface; Brachytherapy; Disease Progression; Gallium Radioisotopes; Gene Expression Regulation, Neoplastic; Glutamate Carboxypeptidase II; Goserelin; Humans; Ligands; Male; Nitriles; Positron-Emission Tomography; Programmed Cell Death 1 Receptor; Prostatectomy; Prostatic Neoplasms, Castration-Resistant; Salvage Therapy; Tosyl Compounds

Topics: Androstenes; Androstenols; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Benzamides; Denosumab; Diphosphonates; Docetaxel; Drug Approval; Drugs, Investigational; Estramustine; Goserelin; Humans; Imidazoles; Male; Mitoxantrone; Nitriles; Oligopeptides; Phenylthiohydantoin; Prostatic Neoplasms; Radioisotopes; Radium; Taxoids; Tissue Extracts; United States; United States Food and Drug Administration; Zoledronic Acid