Therapy of Castleman's disease with siltuximab - case report and review of literature.

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is characterized by constitutional symptoms, enlarged lymph nodes and laboratory test abnormalities, which are primarily related to the overproduction of interleukin-6 (IL-6). This form (iMCD) was treated earlier with cytostatics used for lymphoma, later with bio-logic therapy as rituximab, immunodulatory drugs and proteasome inhibitors, and in the last years with an anti-IL-6 antibody, siltuximab. Siltuximab is a human-mouse chimeric immunoglobulin G1k monoclonal antibody against human IL-6 approved in the European Union for the treatment of iMCD. In view of the limited treatment options for iMCD, this case report aimed to evaluate the efficacy and safety of siltuximab in the management of this condition. CASE: We describe a young woman with iMCD diagnosed at the age of 25 years. For first line treatment, rituximab and dexamethasone were used without any cytostatic because the patient wished to give birth to a healthy child in the future. However, the response after this first line therapy was short. In addition, after 3 years from the start of rituximab + dexamethasone therapy, it was necessary to administer treatment for the relapse of iMCD. We decided for siltuximab in this young woman, still aged < 30 years, and started administration of siltuximab in 3-week intervals. RESULTS: After administration of first two infusions of siltuximab, all inflammatory markers returned to normal value. Moreover, serum hemoglobin and albumin levels as well as C-reactive protein normalized after the first two administrations of siltuximab. The clinical response continue, siltuximab is still administered in 3-week intervals. PET/CT with fluorodeoxyglucose confirmed a very good anatomic and metabolic response to the treatment. Siltuximab demonstrated a favorable safety profile, and the prolonged treatment was well tolerated. CONCLUSION: This result is encouraging and demonstrates the potential of siltuximab as treatment of CD. As earlier published, this case confirms that significantly elevated inflammatory markers in a patient with CD predict a good response to siltuximab.

Alpha emitter radium-223 and survival in metastatic prostate cancer.

BACKGROUND: Radium-223 dichloride (radium-223), an alpha emitter, selectively targets bone metastases with alpha particles. We assessed the efficacy and safety of radium-223 as compared with placebo, in addition to the best standard of care, in men with castration-resistant prostate cancer and bone metastases. METHODS: In our phase 3, randomized, double-blind, placebo-controlled study, we randomly assigned 921 patients who had received, were not eligible to receive, or declined docetaxel, in a 2:1 ratio, to receive six injections of radium-223 (at a dose of 50 kBq per kilogram of body weight intravenously) or matching placebo; one injection was administered every 4 weeks. In addition, all patients received the best standard of care. The primary end point was overall survival. The main secondary efficacy end points included time to the first symptomatic skeletal event and various biochemical end points. A prespecified interim analysis, conducted when 314 deaths had occurred, assessed the effect of radium-223 versus placebo on survival. An updated analysis, when 528 deaths had occurred, was performed before crossover from placebo to radium-223. RESULTS: At the interim analysis, which involved 809 patients, radium-223, as compared with placebo, significantly improved overall survival (median, 14.0 months vs. 11.2 months; hazard ratio, 0.70; 95% confidence interval [CI], 0.55 to 0.88; two-sided P=0.002). The updated analysis involving 921 patients confirmed the radium-223 survival benefit (median, 14.9 months vs. 11.3 months; hazard ratio, 0.70; 95% CI, 0.58 to 0.83; P<0.001). Assessments of all main secondary efficacy end points also showed a benefit of radium-233 as compared with placebo. Radium-223 was associated with low myelosuppression rates and fewer adverse events. CONCLUSIONS: In this study, which was terminated for efficacy at the prespecified interim analysis, radium-223 improved overall survival. (Funded by Algeta and Bayer HealthCare Pharmaceuticals; ALSYMPCA ClinicalTrials.gov number, NCT00699751.).

Preparation and quality control of [166Ho]-macroaggregates for radiosynoviorthesis.

(166)Ho is a beta-emitter (E(_max) = 1.84 MeV, T1/2 = 26.7 hours) with a mean penetration in the soft tissue of 2.2 mm and gamma-photons 81keV and 1380keV. In this paper, we present our experiences with preparation of (166)Ho-macroaggregates ((166)Ho-MA) for radiosynoviorhesis. Ho-MA were prepared by reacting the aqueous solution of holmium nitrate pentahydrate with sodium borohydride solution in 0.2 M NaOH. After centrifugation, washing, and drying at 105 degrees C, final fineness of 1-15 microm was attained using a homogenizer working at 70,000 rpm. Neutron activation was carried out in screwed titanium ampules in a nuclear reactor at the neutron flux 10E12-10E14 neutrons.cm-24.s-1. The irradiated samples were allowed to cool 24 hours before further manipulation. (166)Ho-MA were clinically tested on 20 patients suffering from gonarthrosis (15), rheumatoid arthritis (5), psoriatic arthritis (1), and gout arthropathy (1). (166)Ho-MA are currently produced under GMP and production facility allows producing radioactivity for 6 patients within one production run.