Radium-223 Safety, Efficacy, and Concurrent Use with Abiraterone or Enzalutamide: First U.S. Experience from an Expanded Access Program

Sartor, Oliver; Vogelzang, Nicholas J.; Sweeney, Christopher J.; Fernandez, Daniel C.; Almeida, Fábio; Iagaru, Andrei; Brown, Alan S.; Smith, Matthew R.; Agrawal, Manish; Dicker, Adam P.; García, Jorge A.; Lutzky, Jose; Wong, Yu‐Ning; Petrenciuc, Oana; Gratt, Jeremy; Shore, Neal D.; Morris, Michael J.

doi:10.1634/theoncologist.2017-0413

Cited by 68 publications

(54 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, it is important to emphasise that the majority of our pts started new mCRPC systemic therapy at one month after the end of radium-223 treatment, which was a potential confounder for evaluation of PSA, ALP and disease response in the next months of follow-up. In addition, similar to other reports [30][31][32][33] , pts who had previously been administered abiraterone (35 of 63 pts) did not show evidence of a significant increase in the incidence of skeletal events or relevant toxicity.…”

Section: Discussionsupporting

confidence: 88%

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

Rizzini

Dionisi

Ghedini

et al. 2020

Sci Rep

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 88%

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

Rizzini

Dionisi

Ghedini

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Since its FDA approval and clinical introduction, lots of studies have been carried out concerning the clinical outcomes of 223-Radium dichloride (223-Ra) treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) [6][7][8][9][10][11][12] . Despite this, to our knowledge, at present, it has never been reported the significance and pre-therapeutic prognostic value of previous primary radical treatment in patients treated with 223-Ra therapy.…”

Section: Introductionmentioning

confidence: 99%

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study

Frantellizzi

Costa

Mascia

et al. 2020

Clinical Genitourinary Cancer

View full text Add to dashboard Cite

MicroabstractThis study investigates the impact on the overall survival of previous radical primary treatment in mCRPC patients treated with 223-Ra. In this multicenter retrospective study, we enrolled 275 consecutive patients. Results obtained showed a clear advantage for patients subjected to radical primary treatment in respect of those without, with an estimated median survival of 18 months and 11, respectively. AbstractBackground. We provide an analysis aiming to investigate, in a real-life setting, the prognostic relevance of previous primary treatment (radical prostatectomy (RP) or external beam radiotherapy (EBRT)) in terms of overall survival, in mCRPC patients treated with 223-Ra. Materials and methodsIn this multicenter retrospective study we enrolled 275 consecutive patients. Demographics and clinical data, as well as mCRPC characteristics, have been obtained and evaluated at baseline and the end of the treatment or progression. 223-Ra has been administered according to the current label authorization until disease progression or unacceptable toxicity. We divided the whole cohort into 2 groups: men previously treated with primary radical prostatectomy or ablative radiotherapy (RP/EBRT) and patient with no prior primary treatment available (NO). Results128 out of 275 patients (46.5%) are alive and currently on follow-up; 103 patients (37.4%) dropped treatment out for disease progression or onset of comorbidities, and 147 patients died during the follow-up (53.5%). 93 patients underwent RP, 76 patients performed ablative EBRT. 132 patients enrolled in the RP/EBRT group (48%), 143 patients in the NO group (52%).Data showed a clear advantage for patients subjected to RP or EBRT in respect of those without primary treatment performed, with an estimated median survival of 18 months and 11 respectively (p<0.001). The multivariate analysis corroborated this trending results, returning in an HR of 0.7 (p-value= 0.0443), confirming the best outcome of the RP/EBRT group. 3 Conclusions Previous radical treatment plays a protective role in mCRPC patients who underwent 223-Ra treatment.

show abstract

“…Onkourologiya = Cancer Urology 2019; 15(4): [84][85][86][87][88][89][90][91][92] Диагностика и лечение опухолей мочеполовой системы. Рак предстательной железы препаратов.Былопоказано,чтокакденосумаб,так и золедроновая кислота снижают риск развития костныхпереломовикомпрессииспинногомозга, приэтомденосумабявляетсяболееэффективным [12,13].Оптимальнаяпоследовательностьназначенияуказанныхлекарственныхсредствпокаостается не ясной, однако они совершенно точно должны бытьпримененыдляпрофилактикипереломовупациентов,получающихальфа-терапию.Эмпирически отмечается,чтоначинатьприемостеомодифицирующихагентовследуетзамесяцдовведенияпервой дозырадия-223хлорида.…”

Section: Abstract: Castration-resistant Prostate Cancer Radiopharmaunclassified

Alpha-therapy using radium-223 chloride in patients with castration-resistant prostate cancer. From clinical researches to routine practice

et al. 2020

View full text Add to dashboard Cite

Castration-resistant prostate cancer (CRPC) has a very negative prognosis. The average life expectancy even using modern treatment methods is 1.5–2 years. When the majority of CRPC patients show signs of resistance to therapy aimed at lowering testosterone levels, distant metastases are often determined in the bones. Bone metastases in CRPC patients often worsen life quality due to pain and risk of bone complications, such as pathological fractures and spinal cord compression. Not all treatment regimens to increase their life expectancy patients are effective. Radiopharmacy using alpha-emitting radium-223 chloride is not only one of the methods of palliative treatment, but also one of the most promising therapies that increase life expectancy of these heavy patients. Results of large randomized trials showed that alpha-therapy with radium-223 chloride leads to a significant increase of the overall life expectancy, and significantly improve the patients’ life quality. The article presents literature review as well as the analysis of the results of large randomized trials, which assess the effectiveness of the therapy in CGRG patients, and a clinical case of its use in real clinical practice.

show abstract

Radium-223 Safety, Efficacy, and Concurrent Use with Abiraterone or Enzalutamide: First U.S. Experience from an Expanded Access Program

Cited by 68 publications

References 17 publications

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

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

Primary Radical Prostatectomy or Ablative Radiotherapy as Protective Factors for Patients With mCRPC Treated With Radium-223 Dichloride: An Italian Multicenter Study

Alpha-therapy using radium-223 chloride in patients with castration-resistant prostate cancer. From clinical researches to routine practice

Contact Info

Product

Resources

About