The Clinical Efficacy of Radium-223 for Bone Metastasis in Patients with Castration-Resistant Prostate Cancer: An Italian Clinical Experience

Luca, Rossella De; Costa, Renato; Tripoli, Vincenzo; Murabito, Alessandra; Cicero, Giuseppe

doi:10.1159/000485102

Cited by 18 publications

(17 citation statements)

References 27 publications

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“…As reported in the literature and in our experience, therapy with radium-223 leads to improvement in bone pain 10,27,34 , which favoured dose reduction or discontinuation of pain medication in 12 of our 63 pts; in 38 pts, additional pain medication or dose increase was not needed, while adequate pain control was not achieved in only 8 pts and intensification of pain therapy was required. In the ALYSMPCA trial, 2% of pts in the radium-223 group and 1% of pts in the placebo group had no pain or analgesic use at baseline, and radium-223 treatment favoured less use of opioids compared to placebo 10 .…”

Section: Discussionsupporting

confidence: 66%

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: 66%

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

Rizzini

Dionisi

Ghedini

et al. 2020

Sci Rep

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“…Diagnosis with neuroimaging in the form of MRI with gadolinium is preferred over the traditional method of cerebrospinal fluid (CSF) cytology due to its inferior morbidity for the patient and superior sensitivity (76–87%) [ 5 ]. In castration-resistant prostate cancer with metastatic skeletal disease, radium alpha 223 (a selective calcimimetic bone-seeking radionuclide for bone metastases) has shown a significant benefit with regards to pain reduction and improved quality of life and may be considered as a therapeutic option in patients who continue to progress after docetaxel and prednisone treatment [ 6 ]. Treatment for leptomeningeal disease is palliative with aims to improve quality of life and maintain neurological function, although external beam radiation, systemic, and intra-CSF chemotherapy (via surgical placement of an intraventricular catheter system) are possible [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

“…Recent literature suggests that the incidence of brain and leptomeningeal involvement has increased since the use of docetaxel. Caffo et al proposed that this is due to the inability of docetaxel to penetrate the blood-brain barrier, hence limiting its cerebral concentrations and thus rendering it less effective at eradicating tumour cells from the central nervous system (CNS) [ 6 ]. In the future, such cases may continue to rise secondary to the use of effective modern systemic treatments and prolonged patient survival or improvements in diagnostic techniques [ 3 , 7 - 8 ].…”

Section: Discussionmentioning

confidence: 99%

Leptomeningeal Metastases in Hormone Refractory Prostate Cancer

2018

Cureus

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Leptomeningeal metastases from the prostate are extremely rare, with few cases described in the medical literature (antemortem prevalence of less than 0.03%). Prostatic leptomeningeal metastases harbour a poor prognosis with a median survival after diagnosis of 15.7 weeks. We present the case of an 82-year-old male with a history of hormone-refractory prostate cancer who presented to the emergency department with neurological symptoms.

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“…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

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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.

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The Clinical Efficacy of Radium-223 for Bone Metastasis in Patients with Castration-Resistant Prostate Cancer: An Italian Clinical Experience

Cited by 18 publications

References 27 publications

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

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

Leptomeningeal Metastases in Hormone Refractory Prostate Cancer

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

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