Hematologic Toxicity of Concurrent Administration of Radium-223 and Next-generation Antiandrogen Therapies.

PURPOSE/OBJECTIVES: Radium-223 is a first-in-class radiopharmaceutical recently approved for the treatment of castration-resistant prostate cancer in patients with symptomatic bone metastases. Initial studies investigating Radium-223 primarily used nonsteroidal first-generation antiandrogens. Since that time, newer antiandrogen therapies have demonstrated improved survival in patients with castration-resistant prostate cancer. It has been suggested that the rational combination of these newly approved agents with Radium-223 may lead to improved response rates and clinical outcomes. Currently, there is lack of information regarding the safety of concurrent administration of these agents with radiopharmaceuticals. Here, we report on hematologic toxicity findings from our institution in patients receiving concurrent Radium-223 and next-generation antiandrogen therapies with either enzalutamide or abiraterone. MATERIALS/METHODS: In a retrospective study, we analyzed patients who received Radium-223 as part of an early-access trial, and following FDA approval in May 2013, patients receiving Radium-223 as part of standard care. Radium-223 was given at standard dosing of 50 kBq/kg each month for 6 total cycles. Complete blood counts were performed before treatment monthly and following each injection. Blood counts from patients receiving Radium alone and concurrently with next-generation antiandrogens were compared. To date, 25 total patients were analyzed, with a median of 5 monthly doses received per patient. Fourteen patients received concurrent therapy during monthly Radium-223 with either enzalutamide (n=8) or abiraterone (n=6). RESULTS: Six patients expired due to disease progression. Two patients discontinued treatment due to grade 3 myelosuppression. For patients receiving either Radium alone and with concurrent next-generation antiandrogen therapy, there did not appear to be any statistically significant differences between initial and nadir blood counts. Mean change from initial neutrophil count to nadir was 1.9×10/L in patients receiving Radium alone, versus 2.3×10/L in patients receiving concurrent therapy (P=0.77). Mean change from initial hemoglobin value to nadir was 1.5 g/L in patients receiving Radium alone, versus 1.8 g/L in patients receiving concurrent therapy (P=0.31). Mean change from initial platelet count to nadir was 52.3×10 cells/L in patients receiving Radium alone versus 70.6×10 cells/L in patients receiving concurrent therapy (P=0.39). Individual blood counts for each measured laboratory are included in the supplemental data. PSA was stable or decreased in 22% of patients receiving Radium alone versus 35% of patients receiving combination treatment (P=0.24). CONCLUSIONS: Concurrent administration of Radium-223 and next-generation antiandrogen therapies appears to be well tolerated with similar toxicities to standard administration of Radium-223 alone. This particular cohort of patients represents a high-risk, heavily pretreated group of patients with advanced metastatic disease and significant marrow burden. Despite these risk factors, hematologic toxicity was modest and was in the range expected for this risk group based on previous trials. To date, this is the first study investigating the toxicity of combination treatment. Further studies investigating the safety and efficacy of combination treatments are warranted

Radium ion: A possible candidate for measuring atomic parity violation

Single trapped and laser cooled Radium ion as a possible candidate for measuring the parity violation induced frequency shift has been discussed here. Even though the technique to be used is similar to that proposed by Fortson [1], Radium has its own advantages and disadvantages. The most attractive part of Radium ion as compared to that of Barium ion is its mass which comes along with added complexity of instability as well as other issues which are discussed hereComment: Conference proceedin

Calculations of energy levels and lifetimes of low-lying states of barium and radium

We use the configuration interaction method and many-body perturbation theory to perform accurate calculations of energy levels, transition amplitudes, and lifetimes of low-lying states of barium and radium. Calculations for radium are needed for the planning of measurements of parity and time invariance violating effects which are strongly enhanced in this atom. Calculations for barium are used to control the accuracy of the calculations.Comment: 8 page

Calculation of energy levels and transition amplitudes for barium and radium

The radium atom is a promising system for studying parity and time invariance violating weak interactions. However, available experimental spectroscopic data for radium is insufficient for designing an optimal experimental setup. We calculate the energy levels and transition amplitudes for radium states of significant interest. Forty states corresponding to all possible configurations consisting of the $7s$, $7p$ and $6d$ single-electron states as well as the states of the $7s8s$, $7s8p$ and $7s7d$ configurations have been calculated. The energies of ten of these states corresponding to the $6d^2$, $7s8s$, $7p^2$, and $6d7p$ configurations are not known from experiment. Calculations for barium are used to control the accuracy.Comment: 12 pages, 4 table

Practical recommendations for radium-223 treatment of metastatic castration-resistant prostate cancer

is the first targeted alpha therapy for patients with castration resistant prostate cancer and symptomatic bone metastases. Radium-223 provides a new treatment option for this setting, but also necessitates a new treatment management approach. We provide straightforward and practical recommendations for European nuclear medicine centres to optimize radium-223 service provision. Methods An independent research consultancy agency observed radium-223 procedures and conducted interviews with all key staff members involved in radium-223 treatment delivery in 11 nuclear medicine centres across six countries (Germany, Italy, the Netherlands, Spain, Switzerland and the UK) experienced in administering radium-223. The findings were collated and discussed at a meeting of experts from these centres, during which key consensus recommendations were defined. Results The recommendations cover centre organization and preparation; patient referral; radium-223 ordering, preparation and disposal; radium-223 treatment delivery/administration; and patient experience. Guidance includes structured coordination and communication within centres and multidisciplinary teams, focusing on sharing best practice to provide high quality, patient-centred care throughout the treatment pathway. Conclusions These expert recommendations are intended to complement existing management guidelines. Sharing best practice and experience will help nuclear medicine centres to optimize radium-223 service provision and improve patient care

Chemotherapy following radium-223 dichloride treatment in ALSYMPCA

BACKGROUND Radium-223 prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases, regardless of prior docetaxel. Whether or not chemotherapy can be safely administered following radium-223 treatment is of clinical importance. An exploratory analysis of prospectively collected data, from the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) patient subgroup who received chemotherapy after radium-223 or placebo treatment, was conducted to evaluate the safety and efficacy of chemotherapy following radium-223. METHODS In ALSYMPCA, CRPC patients with symptomatic bone metastases and no visceral metastases were randomized 2:1 to receive six injections of radium-223 (50 kBq/kg IV) or placebo plus best standard of care, stratified by prior docetaxel, baseline alkaline phosphatase, and current bisphosphonate use. In this exploratory analysis, chemotherapy agents administered following study treatment were identified; timing and duration were calculated. Hematologic safety was reviewed, and overall survival analyzed. RESULTS Overall, 142 radium-223 and 64 placebo patients received subsequent chemotherapy; most common were docetaxel (70% radium-223, 72% placebo) and mitoxantrone (16% radium-223, 20% placebo). The majority of patients (61% radium-223, 58% placebo) had received prior docetaxel. Radium-223 patients started subsequent chemotherapy later than placebo patients; chemotherapy duration was similar between groups. In radium-223 and placebo patients receiving subsequent chemotherapy, median hematologic values (hemoglobin, neutrophils, and platelets) remained nearly constant up to 18 months following start of chemotherapy, regardless of prior docetaxel treatment. A low percentage of patients in both groups had grades 3–4 hematologic values (<10%). Platelet count decline, from last measurement before chemotherapy, was numerically greater in radium-223 versus placebo patients. Median overall survivals from start of chemotherapy were 16.0 and 15.8 months following radium-223 and placebo, respectively. CONCLUSIONS Chemotherapy following radium-223, regardless of prior docetaxel, is feasible and appears to be well tolerated in patients with CRPC and symptomatic bone metastases

Development of Physics Applied to Medicine in the UK, 1945–90

Annotated and edited transcript of a Witness Seminar held on 5 July 2005. Introduction by Dr Jeff Hughes.First published by the Wellcome Trust Centre for the History of Medicine at UCL, 2006.©The Trustee of the Wellcome Trust, London, 2006.All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/Annotated and edited transcript of a Witness Seminar held on 5 July 2005. Introduction by Dr Jeff Hughes.Annotated and edited transcript of a Witness Seminar held on 5 July 2005. Introduction by Dr Jeff Hughes.Annotated and edited transcript of a Witness Seminar held on 5 July 2005. Introduction by Dr Jeff Hughes.Annotated and edited transcript of a Witness Seminar held on 5 July 2005. Introduction by Dr Jeff Hughes.Annotated and edited transcript of a Witness Seminar held on 5 July 2005. Introduction by Dr Jeff Hughes.Annotated and edited transcript of a Witness Seminar held on 5 July 2005. Introduction by Dr Jeff Hughes.Organized with the assistance of Professor John Clifton (UCL) and chaired by Professor Peter Williams (Manchester), this seminar examined the early developments of medical physics in the UK between 1945 and 1990. Participants discussed a range of themes including medical physics before and during the war, the role of the King's Fund and the formation of the Hospital Physicists' Association (HPA), expansion of medical physics outside radiotherapy and to non-radiation physics (ultrasound, medical instrumentation, bioengineering, use of digital computers), developing regional services and links with industry. The seminar finished with a discussion on the changing scene in the 1980s, covering topics such as funding, academic and undergraduate medical physics, imaging, CT, NMR and others. Participants included Mr Tom Ashton, Dr Barry Barber, Professors Roland Blackwell and Terence Burlin, Dr Joseph Blau, Mr Bob (John) Burns, Professors John Clifton, David Delpy, Philip Dendy and Jack Fowler, Dr Jean Guy, Mr John Haggith, Drs John Haybittle, Alan Jennings and John Law, Professors John Mallard and Joe McKie, Mr David Murnaghan, Professor Angela Newing, Dr Sydney Osborn, Professor Rodney Smallwood, Dr Adrian Thomas, Dr Peter Tothill, Mr Theodore Tulley, Professors Peter Wells and John West, and Mr John Wilkinson. Christie D A, Tansey E M. (eds) (2006) Development of physics applied to medicine in the UK, 1945–90, Wellcome Witnesses to Twentieth Century Medicine, vol. 28. London: The Wellcome Trust Centre for the History of Medicine at UCL.The Wellcome Trust Centre for the History of Medicine at UCL is funded by the Wellcome Trust, which is a registered charity, no. 210183