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

Boni, Giuseppe; Mazzarri, Sara; Cianci, C.; Galli, Luca; Farnesi, A.; Borsatti, Eugenio; Bortolus, Roberto; Fratino, Lucia; Gobitti, Carlo; Lamaj, Elda; Ghedini, Pietro; Rizzini, Elisa Lodi; Massari, Francesco; Dionisi, Valeria; Fanti, Stefano; Volterrani, Duccio; Monari, Fabio

doi:10.1177/0300891618765571

Cited by 16 publications

(22 citation statements)

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“…This is in line with literature 16,17 and the results from the ALSYMPCA trial in which anaemia as a serious adverse event was reported in 8% of pts with radium-223 and in 9% of pts treated with placebo 10 . It is also in agreement with real-world experience 18 , and in a study in 92 pts with mCRPC only baseline haemoglobin and ECOG PS were www.nature.com/scientificreports www.nature.com/scientificreports/ significantly correlated with OS among all clinical parameters 19 . For this reason, in our opinion, early identification of pts with sideropenic anaemia in which an oral iron supplement was sufficient to restore haemoglobin levels and improve anaemia is mandatory 20,21 .…”

Section: Discussionsupporting

confidence: 89%

Clinical aspects of mCRPC management in patients treated with radium-223

Rizzini

Dionisi

Ghedini

et al. 2020

Sci Rep

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Bone is the most common site of metastasis in metastatic castration-resistant prostate cancer (mCRPC), which is associated with pain and skeletal events. Radium-223 dichloride (Xofigo) is an alphaemitting radioactive isotope that can specifically target bone lesions. Herein, we report the results of a retrospective analysis that documents our experience in the use of radium-223. Data from 63 patients (pts) with mCRPC who underwent radium-223 treatment from December 2015 to September 2017 were collected. Radium-223 (55 kBq/kg) was administered every 4 weeks for up to 6 cycles. The primary endpoint was OS. Radium-223 was administered as first line therapy in 11 pts, as second line in 19 pts, as third line in 16 pts and in successive lines in 17 pts; 42 pts out of 63 (67%) completed all six cycles. Within one month after the end of 6 cycles of radium-223, 15 pts out of 42 (35.7%) had achieved PR, 11 pts out of 42 (26.2%) had SD and 14 pts out of 42 (33.3%) had PD. Levels of pain decreased with progressive cycles of radium-223. After a minimum follow-up of 2 months and a maximum of 43 months, median OS was 15 months and median PFS was 8 months. The most frequent radium-223 related toxicity was low grade haematologic toxicity, predominantly G1-G2, that occurred halfway through treatment in about 75% of pts. The favourable results reported herein confirm that radium-223 can be considered well tolerated and effective in mCRPC, and is associated with significant decreases in pain. Prostate cancer is one of the most commonly diagnosed malignancies and a leading cause of cancer death in men 1. In 2012, there were over 1,000,000 newly diagnosed cases and >307,000 deaths from the disease worldwide 1. In Europe, in 2018, there were an estimated 450,000 new cases of prostate cancer 2 , and in the US, prostate cancer is the second leading cause of cancer deaths following those of the lung and bronchus 3. Even if several treatments are local, including radical prostatectomy, external radiotherapy and brachytherapy, which may allow eradication of disease in some patients (pts), roughly one-third of men will develop distant metastases 4. Even if long-term survival is relatively high, averaging 10 years in those with localised disease, in men with metastatic disease the 5-year survival rate decreases dramatically to approximately 30% 5. Such poor survival rates can be attributed in large part to resistance to treatment in which aggressive variants of prostate cancer arise following the accumulation of mutations in key tumour suppressor genes 6,7. Moreover, androgen depletion is known to induce genes involved in cancer progression and metastasis and the epithelial-to mesenchymal transition, which have implicated the bone-epithelial interaction as a key player in the progression of prostate cancer 8. Bone metastases dominate the clinical picture of advanced prostate cancer and are a major source of morbidity in metastatic disease 9. In pts with recurrence, bone is, in fact, the most common site of metastasis affecting more than 90% o...

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Section: Discussionsupporting

confidence: 89%

Clinical aspects of mCRPC management in patients treated with radium-223

Rizzini

Dionisi

Ghedini

et al. 2020

Sci Rep

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“…Recently, a number of real-life studies provided data regarding the safety and activity of radium-223 in clinical practice, outside of trials. 16–20 We retrospectively collected data from patients with mCRPC, treated at our institution, to assess the safety and activity of radium-223 in a real-world population. These data represent a source of information useful to define a better treatment strategy and improve clinical outcomes in everyday clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Safety and activity of radium-223 in metastatic castration-resistant prostate cancer: the experience of Istituto Nazionale dei Tumori

Raimondi

Sepe

Claps

et al. 2020

Tumori

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Introduction: Therapeutic decision-making in metastatic castration-resistant prostate cancer (mCRPC) represents an open challenge. Radium-223 is approved for patients with symptomatic bone metastases, no visceral involvement, progressing after at least 2 lines of systemic therapy, or ineligible for any other systemic treatment. Methods: We performed a retrospective, observational study on patients with mCRPC treated with radium-223 at our institution outside of clinical trials, to assess the safety and activity in a real-world population. Data regarding baseline patient/disease characteristics and treatment outcomes (number of cycles, treatment-related adverse events [AEs], cause of discontinuation, and best response) were collected. Results: Overall, 41 patients were treated from September 2015 to September 2018. Median age was 73 years; baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS) was 0, 1, or 2 in 15%, 80%, and 5% of cases, respectively; and 3%, 41%, 44%, and 12% of patients had <6, 6–20, >20, and superscan bone lesions, respectively. A median number of 5 cycles (interquartile range 3–6) with median dose 19.52 MBq (interquartile range 12.87–24.83) was received. Treatment schedule was completed in 49% of cases; discontinuations due to AEs, disease-related death, or disease progression occurred in 24%, 33%, and 43% of patients, respectively. Any-grade AEs occurred in 73% and grade 3/4 treatment-related AEs occurred in 29% of patients, mainly anemia, decreased platelet count, and fatigue. No skeletal-related events or treatment-related deaths were recorded. After treatment, 66%, 2%, and 32% of patients had a stable, improved, or deteriorated ECOG PS versus baseline, respectively, and 24%, 61%, and 15% reported a stable, improved, or worsened pain symptom control. Post-treatment versus baseline alkaline phosphatase was reduced or stable in 46% and increased in 54% of patients, whereas prostate-specific antigen was decreased or stable in 83% and increased in 17% of patients. Conclusions: Our study provides clinically useful real-world data on radium-223, highlighting the importance of multidisciplinary patient management to guarantee the best continuum of care for patients with mCRPC.

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“…In their study, the cellular uptake of Radionuclide therapy has become increasingly important for the treatment of malignant tumors. Many new radiotherapy agents for the targeted radiotherapy of tumors have been investigated, including 131 I, 21 233 Ra, 22 and 188 Re. 5 Internal radiotherapy is a viable method for the treatment of unresectable HCC.…”

Section: Discussionmentioning

confidence: 99%

Preliminary Studies of ¹⁷⁷Lu-Diethylenetriamine Penta-Acetic Acid-Deoxyglucose in Hepatic Tumor-Bearing Mice

Zhou

Chen

Yang

et al. 2020

Cancer Biotherapy and Radiopharmaceuticals

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Objective: The purpose of this study was to explore the potential use of 177 Lu-diethylenetriamine penta-acetic acid-deoxyglucose (177 Lu-DTPA-DG) as a radiopharmaceutical for hepatic tumor treatment. Methods: Lutetium-177 (177 Lu) was labeled with DTPA-DG by adding 2 mCi 177 LuCl 3 to 0.05 mg DTPA-DG (pH 5-6) at room temperature for 1 h. The quality of the 177 Lu-DTPA-DG solutions was determined by thinlayer chromatography and high-performance liquid chromatography. Cellular uptake studies with 18 Ffluorodeoxyglucose (FDG), 177 Lu-DTPA-DG and 177 Lu-DTPA and a blocking study with 1.0 mg d-glucose were performed. Biodistribution, imaging, and radiotherapy studies of 177 Lu-DTPA-DG were performed with the SMMC-7721 model. Results: 177 Lu-DTPA-DG had a high radiochemical purity (>97%). The cellular uptake of 177 Lu-DTPA-DG was much higher than that of the 177 Lu-DTPA. The biodistribution of 177 Lu-DTPA-DG demonstrated that the complex accumulated in the tumor with high tumor/blood and tumor/muscle ratios. The tumors in mice in the 177 Lu-DTPA-DG group clearly displayed the high uptake of 177 Lu-DTPA-DG. After radiotherapy with 177 Lu-DTPA-DG, tumor growth decreased, and the overall survival was longer than that in the 177 LuCl 3 group (268.58-17.96 mm 3 vs. 507.43-55.72 mm 3 , p = 0.002) and the normal saline group (268.58-17.96 mm 3 vs. 483.68-27.51 mm 3 , p < 0.05). Conclusions: This preliminary study suggests that 177 Lu-DTPA-DG has the potential to become a liver radiopharmaceutical agent and should be further investigated.

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

Abstract: Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.

Cited by 16 publications

References 23 publications

Clinical aspects of mCRPC management in patients treated with radium-223

Clinical aspects of mCRPC management in patients treated with radium-223

Safety and activity of radium-223 in metastatic castration-resistant prostate cancer: the experience of Istituto Nazionale dei Tumori

Preliminary Studies of ¹⁷⁷Lu-Diethylenetriamine Penta-Acetic Acid-Deoxyglucose in Hepatic Tumor-Bearing Mice

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

Abstract: Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.

Cited by 16 publications

References 23 publications

Clinical aspects of mCRPC management in patients treated with radium-223

Clinical aspects of mCRPC management in patients treated with radium-223

Safety and activity of radium-223 in metastatic castration-resistant prostate cancer: the experience of Istituto Nazionale dei Tumori

Preliminary Studies of 177Lu-Diethylenetriamine Penta-Acetic Acid-Deoxyglucose in Hepatic Tumor-Bearing Mice

Contact Info

Product

Resources

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

Preliminary Studies of ¹⁷⁷Lu-Diethylenetriamine Penta-Acetic Acid-Deoxyglucose in Hepatic Tumor-Bearing Mice