Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial

Parker, Christopher; Coleman, Robert E.; Sartor, Oliver; Vogelzang, Nicholas J.; Bottomley, David; Heinrich, Daniel; Helle, Svein Inge; O’Sullivan, Joe M.; Fosså, Sophie D.; Chodacki, Aleš; Wiechno, Paweł; Logue, John P; Seke, Mihalj; Widmark, Anders; Johannessen, Dag Clement; Hoskin, Peter; James, Nicholas D.; Solberg, Arne; Syndikus, Isabel; Kliment, J.; Wedel, Steffen; Boehmer, S.; Dall’Oglio, Marcos F.; Franzén, Lars; Bruland, Øyvind S.; Petrenciuc, Oana; Staudacher, K.; Li, Rui; Nilsson, Sten

doi:10.1016/j.eururo.2017.06.021

Cited by 88 publications

(59 citation statements)

References 18 publications

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“…Although we cannot rule out the contribution of radium-223 therapy to the increase in anaemia seen in our sample, we can say that pts with lower haemoglobin levels at the start of therapy because of a higher number of metastases, had a similar trend in haemoglobin levels during radium-223 treatment with an adequate supportive care for anaemia than pts with fewer metastases. 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 .…”

Section: Discussionsupporting

confidence: 91%

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: 91%

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

Rizzini

Dionisi

Ghedini

et al. 2020

Sci Rep

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“…In ALSYMPCA, radium-223 was also associated with a significantly prolonged time to symptomatic skeletal events (SSEs) and reduced alkaline phosphatase (ALP) levels vs placebo ( p < 0.001 for both), and was well tolerated [ 11 ]. In addition, no second primary treatment-related malignancies were reported when patients were followed for up to 3 years [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Three-year follow-up of a phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer and bone metastases

Uemura

Nagamori

et al. 2019

Int J Clin Oncol

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Background Radium-223 is a first-in-class targeted alpha therapy to prolong overall survival (OS) in castration-resistant prostate cancer with bone metastases (mCRPC). The aim of the present analysis was to assess the long-term safety with radium-223 in Japanese patients with mCRPC. Methods Patients with symptomatic mCRPC, ≥ 2 bone metastases and no known visceral metastases received up to 6 injections of radium-223 (55 kBq/kg), one every 4 weeks. Adverse events (AEs) considered to be related to radium-223 were reported until 3 years after the first injection. Pre-specified conditions, such as acute myelogenous leukemia, myelodysplastic syndrome, aplastic anemia, primary bone cancer, or other primary malignancies, were reported regardless of causality. Results Of the 49 patients enrolled in the study, 44 (89.8%) entered the survival follow-up period and 33 (67.3%) died. Throughout the entire study, there were no reports of second primary malignancy or other pre-specified conditions. Eight patients (16.3%) experienced post-treatment drug-related AEs, which were all hematological (anemia and decreased lymphocyte, platelet, and white blood cell counts). No serious post-treatment drug-related AEs were reported. Updated median OS was 19.3 months (95% CI: 14.2, 28.5). Conclusions In Japanese patients with symptomatic mCRPC and bone metastases, radium-223 had a favorable long-term safety profile with no second primary malignancies reported. Taken together with median OS, which was comparable to that in the pivotal phase III ALSYMPCA study, these results support continued benefit from radium-223 in Japanese patients with mCRPC. Electronic supplementary material The online version of this article (10.1007/s10147-018-01389-4) contains supplementary material, which is available to authorized users.

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“…With regard to all hematologic adverse events, thrombocytopenia was more prevalent in the Xofigo group (12%) compared to the placebo group (6%), and neutropenia was also more prevalent in the Xofigo group (5%) compared to placebo (1%). Anemia had the same prevalence in the Xofigo group and placebo (31% and 31%, respectively) [10].…”

Section: Discussionmentioning

confidence: 81%

A Single-center Retrospective Analysis of the Effect of Radium-223 (Xofigo) on Pancytopenia in Patients with Metastatic Castration-resistant Prostate Cancer

Skelton

Dibenedetto

Pang

et al. 2020

Cureus

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Introduction Radium-223 (Xofigo, Bayer Pharmaceuticals Inc., Whippany, NJ) has been shown to increase overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC), via the phase 3 ALpharadin in SYMPtomatic Prostate CAncer (ASLYMPCA) study. Hematologic side effects of radium-223 included all-grade anemia in 31% of the patients, thrombocytopenia in 12%, and neutropenia in 5%, and persistent pancytopenia noted in 2%. However, the incidence seen in our institutional clinical practice is higher than that reported in the literature. Methods A retrospective analysis was performed by analyzing patients with mCRPC who received Xofigo at the University of Florida Health Shands Hospital (UF Health Shands) in a three-year span. Data collected included complete blood count (CBC), ECOG (Eastern Cooperative Oncology Group) functional status, kidney and liver function, evidence of bony disease on imaging, prior chemotherapy regimens, total radiation dose, and prostate-specific antigen (PSA). Results Twenty-three patients received Xofigo at UF Health, and one was lost to follow-up. Sixteen patients (73%) completed the full course (six doses) of Xofigo, while six did not. Ten patients (45%) developed pancytopenia, with two recovering counts within eight months while the other eight had persistent cytopenias (six of which were transfusion-dependent). Older age and higher ECOG score correlated with increased risk of pancytopenia. In addition, a higher percentage of patients who received prior radiation therapy were more likely to develop pancytopenia (90% vs 75%). Conclusions We found a higher rate of Xofigo-induced pancytopenia in our patient population than the 2% reported in the literature, albeit with a limited sample size, This may influence clinical decision making in the treatment of mCRPC, as pancytopenia may preclude patients from other survival-prolonging therapies. Factors such as age, functional status, and prior radiation therapy have to be considered prior to Xofigo treatment.

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Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial

Abstract: Updated Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial findings show that radium-223 remained well tolerated during treatment and up to 3 yr after each patient's first injection.

Cited by 88 publications

References 18 publications

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

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

Three-year follow-up of a phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer and bone metastases

A Single-center Retrospective Analysis of the Effect of Radium-223 (Xofigo) on Pancytopenia in Patients with Metastatic Castration-resistant Prostate Cancer

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