Re-treatment with radium-223: 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases.

BACKGROUND: Radium-223 dichloride (radium-223) is approved for patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open-label, phase 1/2 study NCT01934790 showed that re-treatment with radium-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2-year follow-up of the radium-223 re-treatment study. METHODS: Patients with CRPC and bone metastases who completed 6 initial radium-223 injections with no disease progression in bone and later progressed were eligible for radium-223 re-treatment (up to 6 additional radium-223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium-223. Concomitant cytotoxic agents were not allowed during re-treatment but were allowed at the investigator's discretion during follow-up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression-free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate-specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-treatment start. Evaluation of safety and exploratory efficacy objectives included active 2-year follow-up. Safety results from active follow-up and updated efficacy are reported. RESULTS: Overall, 44 patients were re-treated with radium-223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2-year active follow-up, during which no new safety concerns and no serious drug-related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months. CONCLUSIONS: Re-treatment with radium-223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up.

Cytologic diagnosis of chordoma in a peritoneal effusion: a case report.

BACKGROUND: Chordoma, a distinct malignant neoplasm arising from the remnants of the notochord, occurs mostly in patients in the fifth to seventh decade of life. Metastasis occurs in 20-30% of cases. The most common metastatic sites are lungs and, less commonly, other bones and visceral organs. The cytologic features of chordoma in both primary and metastatic foci have been described for specimens obtained by fine needle aspiration biopsy. A few cases have been reported in the sputum and the cerebrospinal fluid. CASE: A 57-year-old man presented with metastatic chordoma diagnosed in a peritoneal effusion. Cytospin slides of the effusion showed numerous individual and clusters of polygonal, round epithelial cells with a background of myxoid chondroid substance, which stained metachromatic on Diff-Quik slides. Many diagnostic physaliphorous cells were present and characterized by abundant intracytoplasmic vacuoles of various sizes. The nuclei were monotonous, with minimal anisonucleosis. The nuclei had evenly dispersed chromatin with occasional small, eosinophilic nucleoli. The nuclear membranes were smooth, with focal indentation. The differential diagnosis included an adenocarcinoma and metastatic chordoma. Immunohistochemistry applied to the cell block showed that the neoplastic cells were positive for cytokeratin and S-100 protein. CONCLUSION: The clinical history with immunohistochemical profiles helped confirm the diagnosis of metastatic chordoma.

Contemporary pharmacotherapy for the prevention of skeletal complications in patients with prostate cancer.

INTRODUCTION: Bones represent the most common metastatic sites in prostate cancer (PCa) patients, and in addition with androgen deprivation therapy, they represent the causative reasons of bone mineral density loss and the onset of skeletal-related events. AREAS COVERED: An extensive search of PubMed/Medline was performed to identify randomized, Phase II/III controlled trials reporting results regarding the prevention of skeletal morbidity in patients with PCa. EXPERT OPINION: Preventing bone health is an imperative issue for preserving quality of life and elongate survival and, thus, a concerted effort should be made to monitor skeletal changes and to apply treatment for preventing bone loss. Although several agents have received approval for routine use, it is of paramount importance to identify the appropriate patients who would mostly be benefited by the use of these agents with attention to documenting the toxicity and economic implications. Additionally, it remains to be justified the frequency of administration in order to balance the efficacy and the potential complications.