Bone pain palliation outcomes and possibility of Radium-223 re-treatment in mCRPC

Objective. Bone secondary localizations from metastatic castration-resistant prostate cancer are associated with an increase in mortality and a reduction in the patient’s quality of life. Radium-223 is a targeted alpha-therapy approved for the treatment of mCRPC (metastatic castration resistant prostate cancer) patients with symptomatic bone metastases. To our knowledge, no previous study has been performed assessing the bone pain palliation outcomes following Radium-223 therapy. Materials and Methods. A mCRPC patient with symptomatic bone localizations and relevant bone pain symptoms has been subjected to Radium-223 treatment. Pain was assessed over time from the first administration of Radium-223 to follow-up. Results. After Radium-223 treatment, patient showed a significant BPI (Brief Pain Inventory) decline from 7 to 4 and a concomitant partial regression of multiple bone hot spots in the bone scan exam. Three months after the last infusion of Radium-223, further BPI decline (from 4 to 2) with bone scan depicting stable disease was observed. However, after 6 months from Radium-223 treatment end, BPI increased from 2 to 10. Conclusions. Taking into account the effectiveness on bone pain relief and the low toxicity profile showed by Radium-223 treatment, we encourage further analysis on large cohort to investigate the clinical outcome after Radium-223 treatment, in terms of bone pain palliation, together with the possibility of Radium-223 re-treatment in selected patients..

Targeted Palliative Radionuclide Therapy for Metastatic Bone Pain

Bone metastasis develops in multiple malignancies with a wide range of incidence. The presence of multiple bone metastases, leading to a multitude of complications and poorer prognosis. The corresponding refractory bone pain is still a challenging issue managed through multidisciplinary approaches to enhance the quality of life. Radiopharmaceuticals are mainly used in the latest courses of the disease. Bone-pain palliation with easy-to-administer radionuclides offers advantages, including simultaneous treatment of multiple metastatic foci, the repeatability and also the combination with other therapies. Several β¯- and α-emitters as well as pharmaceuticals, from the very first [89Sr]strontium-dichloride to recently introduced [223Ra]radium-dichloride, are investigated to identify an optimum agent. In addition, the combination of bone-seeking radiopharmaceuticals with chemotherapy or radiotherapy has been employed to enhance the outcome. Radiopharmaceuticals demonstrate an acceptable response rate in pain relief. Nevertheless, survival benefits have been documented in only a limited number of studies. In this review, we provide an overview of bone-seeking radiopharmaceuticals used for bone-pain palliation, their effectiveness and toxicity, as well as the results of the combination with other therapies. Bone-pain palliation with radiopharmaceuticals has been employed for eight decades. However, there are still new aspects yet to be established.

[177Lu]Lu-DOTA-ZOL Bone Pain Palliation in Patients with Skeletal Metastases From Various Cancers: Efficacy and Safety Results

Background: [177Lu]Lu-DOTA-ZOL has shown promising results from the dosimetry and preclinical aspects, but data on its role in the clinical efficacy is limited. In this light, the objective of this study is to evaluate the efficacy and safety of [177Lu]Lu-DOTA-ZOL as a bone pain palliation agent in patients experiencing pain due to skeletal metastases from various cancers.Methods: 40 patients experiencing bone pain due to skeletal metastases were enrolled in this study. The patients were treated with a mean cumulative dose of 2.1 ± 0.6 GBq (1.3–2.7 GBq) [177Lu]Lu-DOTA-ZOL in a median follow-up duration of 10 months (IQR: 8–14 months). The primary outcome endpoint was response assessment according to the visual analog score (VAS). Secondary endpoints included analgesic score (AS), global assessment pain score, Eastern Cooperative Oncology Group Assessment performance status (ECOG), Karnofsky Performance Status (KPS), overall survival, and safety assessment by the National Cancer Institute’s Common Toxicity Criteria V5.0.Results: 40 patients, 15 males, and 25 females with a mean age of 46.6 ± 15.08 years (range: 24–78 years) were treated with either 1 (N = 15) or 2 (N = 25) cycles of [177Lu]Lu-DOTA-ZOL. According to the VAS response assessment criteria, complete, partial, and minimal responses were observed in 11 (27.5%), 20 (50%), and 5 patients (12.5%), respectively with an overall response rate of 90%. Global pain assessment criteria revealed complete, partial, minimal and no response in 2 (5%), 25 (62.5%), 9 (22.5%), and 4 (10%) patients, respectively. Twenty eight patients died and the estimated median overall survival was 13 months (95% CI: 10–14 months). A significant improvement was observed in the VAS, AS and ECOG status when compared to baseline. None of the patients experienced grade III/IV hematological, kidney or hepatotoxicity due to [177Lu]Lu-DOTA-ZOL therapy.Conclusion: [177Lu]Lu-DOTA-ZOL shows promising results and is an effective radiopharmaceutical in the treatment of bone pain due to skeletal metastases from various cancers.