Treatment of Osteoblastic Skeletal Metastases by the Alpha-Emitting Bone-Seeker Radium-223

2013 ◽  
pp. 447-457
Author(s):  
Øyvind S. Bruland ◽  
Roy H. Larsen
Keyword(s):  
Skeletal Metastases ◽  
Radium 223

Cause of radium 223 treatment discontinuation in elderly mCRPC patients.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 376-376
Author(s):  
Renato Patrizio Costa ◽  
Fabio Raiti ◽  
Sebastiano Bordonaro ◽  
Vincenzo Tripoli ◽  
Alessandra Murabito ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Real Life ◽  
The Elderly ◽  
Treatment Discontinuation ◽  
Cancer Center ◽  
Skeletal Metastases ◽  
Hematologic Toxicity ◽  
Radium 223 ◽  
Number Of Patients

376 Background: Prostate cancer is the most common cancer among adult men. Bones are the main metastatic site of prostate cancer. Radium-223 is indicated to treat metastatic castrate-resistant prostate cancer ( mCRPC) with symptomatic skeletal metastases. We evaluate the tolerability of Ra223 treatment in real life setting. Methods: We reported the cases of 38 consecutive non-selected patients with mCRPC symptomatic bone metastases treated in two Italian hospital cancer center from August 2016 to October 2017. The cause of Ra 223 treatment discontinuation in elderly prostate cancer patients were evaluated. Results: due bones metastases, 38 patients were treated with Radium-223; 20 were ≥75 years old (range 75-85 yrs). Patients characteristics and main toxicity are reported (Table). Regarding the elderly patients, hematologic toxicity were the most common adverse events reported. Anemia G2-G3 was observed in 10 pts (50%), thrombocytopoenia G3 in 2 patients (10%) and neutropenia G3 in 4 patients (20%); 12/20 patients interrupted the treatment, of which 10 were ECOG PS2. The number of patients who discontinued the drug because of hematologic adverse events was higher than ALSYMPCA clinical trial. Fatigue G1-G2 incidence was 32%. Unexpectedly we did not record any cases of gastrointestinal toxicity (diarrhea, nausea or constipation). Conclusions: In patients ≥75 years old, anemia G2-G3 was more frequent than data reported in literature, while diarrhea is not found. The data of this experience suggest that elderly vulnerable patients are more exposed to hematologic toxicity that may compromise the outcome of the treatment. For these patients surveillance for early supportive care is relevant. Characteristics of patients with ≥75y. [Table: see text]

Alpha-Emitter Radium-223 in the Management of Solid Tumors: Current Status and Future Directions

2014 ◽  
pp. e132-e139 ◽  
Author(s):  
Sten Nilsson
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Bone Metastases ◽  
High Energy ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
Current Status ◽  
Skeletal Metastases ◽  
Radium 223 ◽  
Alpha Emitter

Bone metastases, which are commonly seen in patients with advanced cancers, are a major cause of skeletal events, disability, and death. Radium-223 dichloride (radium-223; Xofigo, formerly Alpharadin), a first-in-class, alpha-emitting radiopharmaceutical that selectively targets bone metastases with high-energy short-range alpha-particles, has been approved for the treatment of patients with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastases. Approval is based on results of the randomized phase III trial Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA), in which radium-223 prolonged overall survival and time to first symptomatic skeletal event versus placebo among patients with CRPC with symptomatic bone metastases and was generally well tolerated, with low myelosuppression rates and manageable gastrointestinal adverse events. Long-term follow-up of the ALSYMPCA safety population showed that the incidence of myelosuppression remained low among patients treated with radium-223, with no additional safety issues of acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, or primary bone cancer within approximately 1.5 years after treatment. The radium-223 overall survival benefit and low toxicity make it an effective, well-tolerated, and novel treatment option for CRPC and symptomatic bone metastases and opens the possibility of exploring radium-223 in the treatment of bone metastases from other cancers. A phase I clinical trial of patients with breast and prostate cancer with skeletal metastases demonstrated that radium-223 was safe and well tolerated at all therapeutically relevant dosages. Moreover, a phase IIa trial of patients with advanced breast cancer and progressive bone-dominant disease demonstrated that radium-223 targeted areas of increased bone metabolism and showed biologic activity.

scholarly journals First Clinical Experience with α-Emitting Radium-223 in the Treatment of Skeletal Metastases

2005 ◽  
Vol 11 (12) ◽  
pp. 4451-4459 ◽  
Author(s):  
Sten Nilsson ◽  
Roy H. Larsen ◽  
Sophie D. Fosså ◽  
Lise Balteskard ◽  
Kari W. Borch ◽  
...  
Keyword(s):  
Clinical Experience ◽  
Skeletal Metastases ◽  
Radium 223

223Ra-chloride therapy in men with hormone-refractory prostate cancer and skeletal metastases: Real-world experience

2018 ◽  
Vol 104 (2) ◽  
pp. 128-136 ◽  
Author(s):  
Giuseppe Boni ◽  
Sara Mazzarri ◽  
Claudia Cianci ◽  
Luca Galli ◽  
Azzurra Farnesi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Rating Scale ◽  
Therapeutic Option ◽  
Progression Free Survival ◽  
Numeric Rating Scale ◽  
Skeletal Metastases ◽  
Castration Resistant Prostate Cancer ◽  
Radium 223 ◽  
Alpha Emitter ◽  
Skeletal Related Events

Background: Radium-223 (223Ra) chloride, an alpha emitter, has been shown to improve overall survival (OS) and pain control, and to delay skeletal-related events, in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Our retrospective observational study presents the first Italian experience on the efficacy and safety of 223Ra therapy in routine clinical practice. Methods: A total of 83 patients with metastatic CRPC were treated with 223Ra at 3 Italian centers between August 2013 and August 2016. 223Ra-chloride (55 kBq/kg) was administered every 4 weeks for a total of 6 cycles. Primary endpoints were OS and progression-free survival (PFS). Secondary endpoints included toxicity, pain evaluation using numeric rating scale (NRS), symptomatic skeletal-related events and biomarkers response. Results: Patients had a median age of 75 (range 53–89) years. The majority of men showed a Gleason score of 7, 8, or 9. Forty-one patients completed 6 treatment cycles; 33 stopped treatment before completing 6 cycles. Nine were still receiving therapy at the time of data collection. At the end of therapy, NRS pain scores significantly improved ( p < .000001). OS was a mean of 10.1 months, while median OS had not been attained. According to Kaplan-Meier estimation, OS and PFS were 17.5 and 7.7 months, respectively. There was a significant correlation between OS and PFS with the number of 223Ra cycles; patients receiving all 6 cycles experienced the major benefit from the therapy. 223Ra was well-tolerated. Conclusions: 223Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.

Targeted Radionuclide Therapy of Painful Bone Metastases: Past Developments, Current Status, Recent Advances and Future Directions

2020 ◽  
Vol 27 (19) ◽  
pp. 3187-3249 ◽  
Author(s):  
Ashutosh Dash ◽  
Tapas Das ◽  
Furn F. Russ Knapp
Keyword(s):  
Bone Metastases ◽  
Radionuclide Therapy ◽  
Bone Pain ◽  
Progression Free Survival ◽  
Current Status ◽  
Skeletal Metastases ◽  
Ionic Form ◽  
Castration Resistant Prostate Cancer ◽  
Recent Advances ◽  
Radium 223

Bone pain arising from secondary skeletal malignancy constitutes one of the most common types of chronic pain among patients with cancer which can lead to rapid deterioration of the quality of life. Radionuclide therapy using bone-seeking radiopharmaceuticals based on the concept of localization of the agent at bone metastases sites to deliver focal cytotoxic levels of radiation emerged as an effective treatment modality for the palliation of symptomatic bone metastases. Bone-seeking radiopharmaceuticals not only provide palliative benefit but also improve clinical outcomes in terms of overall and progression-free survival. There is a steadily expanding list of therapeutic radionuclides which are used or can potentially be used in either ionic form or in combination with carrier molecules for the management of bone metastases. This article offers a narrative review of the armamentarium of bone-targeting radiopharmaceuticals based on currently approved investigational and potentially useful radionuclides and examines their efficacy for the treatment of painful skeletal metastases. In addition, the article also highlights the processes, opportunities, and challenges involved in the development of bone-seeking radiopharmaceuticals. Radium-223 is the first agent in this class to show an overall survival advantage in Castration-Resistant Prostate Cancer (CRPC) patients with bone metastases. This review summarizes recent advances, current clinical practice using radiopharmaceuticals for bone pain palliation, and the expected future prospects in this field.

Radium 223 treatment in metastatic prostate cancer: Exploring use of clinical factors for prognostication in routine practice.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17550-e17550
Author(s):  
Salil Vengalil ◽  
Paula Bee ◽  
Dawn Beetham ◽  
Rajanee Bhana ◽  
Shibu Joseph ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Skeletal Metastases ◽  
Routine Practice ◽  
Poor Overall Survival ◽  
Median Baseline ◽  
Radium 223 ◽  
Retrospective Audit ◽  
Alpha Emitter ◽  
Normal Albumin

e17550 Background: Skeletal metastases are seen in over 90% of metastatic castrate resistant prostate cancer (mCRPC) patients during the course of their disease and is a major cause for significant morbidity and mortality in them. Radium 223 (Ra-223) is a bone seeking calcium mimetic alpha emitter that has demonstrated significant improvement in survival and reduction in skeletal related events (ALSYMPCA trial). Ra-223 treatment was well tolerated and showed benefit before or after chemotherapy. In this study we aimed to assess efficacy of Ra-223 in mCRPC patients treated in our centre and their survival in relation to some common clinical variables that may assist patient selection in routine clinical practice. Methods: We conducted a retrospective audit of mCRPC patients treated with Ra-223 from June 2015 – December 2019. We analysed treatment outcomes and use of Haemoglobin (Hb), Albumin (Alb) and Alkaline Phosphatase (ALP) as potential prognostic factors. Results: There were 46 patients in total with a median age of 76 years (range; 56-90) and 26% were ≥80 years of age. The median follow-up was 10 months (range; 2-38 months). Median baseline PSA was 103.7 (range; 7.2 - 2534) and median baseline ALP was 188 U/L (range; 51 - 2262). Ra-223 was given as 1st or 2nd line treatment in 65% of our patients. Median number of cycles of Ra-223 administered was 4 and 41% of patients completed 6 cycles of treatment. Biochemical response (drop in PSA > 50%) was only seen in 11% of patients but good response in ALP levels (drop in ALP > 50%) was seen in 35%. Median overall survival (OS) was 10 months. Median OS for patients who received Ra-223 as 1st or 2nd line vs subsequent line was 13 and 8.5 months respectively. Median OS for patients with Haemoglobin (Hb) ≥12gm/dl) and lower Hb were 11 and 7 months respectively. Patients with normal albumin at baseline had median OS of 15 months compared to 6 months for those with low albumin. Favourable prognostic group patients (Normal Hb, Normal albumin at baseline and normal ALP after treatment) had a median OS of 31 months compared to 9 months for those in less favourable group. Patients who completed at least 5 cycles had a better survival (13 vs 8.5 months). Fractures were reported in 3 patients (6.5%). Conclusions: Ra-223 treated patients in our centre had a reasonable survival despite having a larger proportion of elderly population compared to the registration trial. Ra-223 treatment seems to be more effective when given at earlier lines in mCRPC setting. Pre-treatment Albumin lower than normal seems to be a predictor for poor overall survival.

scholarly journals A novel tool for improving the interpretation of isotope bone scans in metastatic prostate cancer

2020 ◽  
Vol 93 (1115) ◽  
pp. 20200775
Author(s):  
ALI H.D. Alshehri ◽  
Sarah O.S. Osman ◽  
Kevin M. Prise ◽  
Caoimhghin Campfield ◽  
PG Turner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Clinical Utility ◽  
Bone Scan ◽  
Metastatic Prostate Cancer ◽  
Imaging Modality ◽  
Skeletal Metastases ◽  
Bone Lesions ◽  
Subjective Interpretation ◽  
Radium 223

Objectives: The isotope bone scan (IBS) is the gold-standard imaging modality for detecting skeletal metastases as part of prostate cancer staging. However, its clinical utility for assessing skeletal metastatic burden is limited due to the need for subjective interpretation. We designed and tested a novel custom software tool, the Metastatic Bone Scan Tool (MetsBST), aimed at improving interpretation of IBSs, and compared its performance with that of an established software programme. Methods: We used IBS images from 62 patients diagnosed with prostate cancer and suspected bone metastases to design and implement MetsBST in MATLAB by defining thresholds used to identify the texture and size of metastatic bone lesions. The results of MetsBST were compared with those of the commercially available automated Bone Scan Index (aBSI) with regression analysis. Results: There was strong agreement between the MetsBST and aBSI results (R2 = 0.9189). In a subregional analysis, MetsBST quantified the extent of metastatic disease in multiple bone sites in patients receiving multimodality therapy (radium-223 and external beam radiotherapy) to illustrate the differences in bone metastatic response to different treatments. Conclusion: The results of MetsBST and the commercial software aBSI were highly consistent. MetsBST introduces novel clinical utility by its ability to differentiate between the responses of different bone metastases to multimodality therapies. Advances in knowledge: MetsBST reduces the variability in assessment of tumour burden caused by subjective interpretation. Therefore, it is a useful aid to physicians reporting nuclear medicine scans, and may improve decision-making in the treatment of metastatic prostate cancer.

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