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

Abstract

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.

Combined Bone Scintigraphy and Fluorocholine PET/computed Tomography Predicts Response to radium-223 Therapy in Patients With Prostate Cancer

“…This is in accordance with the poor effect of 223 radium in osteolytic lesions (MDP negative) observed in thyroid cancer patients [33] and could explain the worse outcome of patients with more lesions detected by 18 F-fluorocholine PET/CT compared with bone scintigraphy. Regarding patients' reported pain, consistently with previous real-world data [34], 56 and 35% of patients reported an improvement and a stabilization of pain at the end of the treatment, respectively. Patients who did not have pain relief had a significantly higher prevalence of pretherapy mismatch between imaging methods with more lesions detected at PET/CT, confirming that 223 radium accumulates in osteoblastic metastases and exerts its therapeutic action on these lesions.…”

Safety and effectiveness of the radium‐223–taxane treatment sequence in patients with metastatic castration‐resistant prostate cancer in a global observational study (REASSURE)

“…These findings are consistent with the results from an exploratory analysis of the phase 3 ALSYMPCA trial in patients who received chemotherapy (primarily docetaxel) after radium‐223 treatment 6 ; in that analysis, approximately 10% of patients had grade 3/4 hematologic laboratory abnormalities up to 18 months after the first chemotherapy cycle 6 . Other prospective observational studies and retrospective analyses in patients with mCRPC provide evidence of the favorable safety profile of radium‐223 in real‐world settings, with a generally low incidence of myelosuppression 14–19 …”

“…6 Other prospective observational studies and retrospective analyses in patients with mCRPC provide evidence of the favorable safety profile of radium-223 in real-world settings, with a generally low incidence of myelosuppression. [14][15][16][17][18][19] Notably, the 182 patients in our analysis received taxane chemotherapy for 3.7 months on average, which equates to six 3weekly cycles. For context, although patients received up to 10 cycles of docetaxel as first-line therapy in the pivotal TAX-327 study, 1 in the exploratory ALSYMPCA analysis, the median duration of first post-radium-223 chemotherapy was 4.6 months 6 ; in addition, in a real-world analysis of US electronic health records, the median duration of docetaxel therapy for mCRPC was 4.1 months in the second line and 3.8 months in the third line.…”

Investigation of the Disparities in Ultrasound Imaging Features of miR-323, miR-409-3p, and VEGF Expression Scales in Different Clinicopathological Features of Prostate Carcinoma and Their Correlation with Prognosis

“…Sufferers usually have symptoms such as frequent urination and urgency, which seriously affects their daily life [ 1 ]. For the therapy of prostate carcinoma sufferers, radical prostatectomy is used clinically to remove the diseased prostate tissue and rebuild the sufferer's urinary pathway, but there is still a risk of recurrence after surgery [ 2 ]. Therefore, it is of expensive clinical value to evaluate the prognosis of sufferers with prostate carcinoma early and to formulate prevention and therapy plans according to the evaluation results, so as to avoid the risk of recurrence and ensure the prognosis.…”