Use of radionuclides in metastatic prostate cancer: Pain relief and beyond
Bone metastases in prostate cancer are often the cause of significant morbidity in patients with castrate-resistant disease, and several studies have shown significant pain palliation with systemic radionuclide treatment. The purpose of this review is to discuss the place of radionuclides in the dynamic treatment landscape of metastatic prostate cancer in light of new evidence demonstrating benefit beyond palliation.
The recently reported ALSYMPCA trial, which was a multicentre, placebo-controlled, phase 3 randomized controlled trial in patients with symptomatic metastatic castrate-resistant prostate cancer (CRPC) has shown significant overall survival (OS) benefit in favour of Radium-223 (Alpharadin) treatment [median OS 14.0 vs. 11.2 months; P = 0.00185; hazard ratio 0.695; 95% confidence interval (CI) 0.552-0.875]. This situation led to early unblinding of the trial and patients on placebo arm being offered Radium-223 treatment.
It has been an exciting and challenging time for treatment of patients with metastatic CRPC with six new agents demonstrating OS benefit in phase 3 trials, in this setting since 2004. Further research should focus on appropriate sequencing and innovative strategies to use these therapeutic agents to maximize benefit for patients. In the case of radionuclides, novel strategies include repeated administration, dose intense regimens and combination with other agents.
Available from: Candice Johnstone
- "Strontium-89 (89Sr) chloride and 153Sm lexidronam are radiopharmaceuticals currently approved in the US and Europe for palliation of bone metastases. Rhenium-186 (186Re) hydroxyethylidene diphosphonate (HEDP), 188Re HEDP, and radium-223 (223Ra) dichloride are currently under investigation.1,8,12,13 "
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ABSTRACT: Bone metastases are prevalent among cancer patients and frequently cause significant morbidity. Oncology providers must mitigate complications associated with bone metastases while limiting therapy-related adverse effects and their impact on quality of life. Multiple treatment modalities, including chemotherapy, surgery, external beam radiation therapy, and radioisotopes, among others, have been recommended and utilized for palliative treatment of bone metastases. Radioisotopes such as samarium-153 are commonly used in the setting of multifocal bone metastases due to their systemic distribution, affinity for osteoblastic lesions, acceptable toxicity profile, and convenience of administration. This review focuses on samarium-153, first defining its radiobiologic and pharmacokinetic properties before describing many clinical trials that support its use as a safe and effective tool in the palliation of patients with bone metastases.
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ABSTRACT: Secondary bone tumors associated with the advancement of solid tumors of the prostate and other tissue sites result in the increased risk of intractable bone pain, pathological skeletal fracture and spinal-cord compression. In addition to increasing morbidity the occurrence of metastatic bone lesions results in a marked reduction in patient survival. Once lesions have established in the bone the disease is able to progress by homotypic and heterotypic cellular interactions between the invading tumor cells and bone-associated osteoblasts and osteoclasts. The vicious cycle of bone matrix remodeling that ensues in lesions with an osteolytic phenotype is largely driven by increased osteoclast-mediated bone degradation - which leads to the subsequent loss of normal bone structure and compromised bone strength. In prostate cancer there is the additional complication of a predominantly osteosclerotic lesion phenotype - where osteoblasts become activated to overproduce a highly disorganized new bone matrix. Advances have been made in the treatment of osteolytic bone lesions - for which the currently approved treatment is the delivery of intravenous bisphosphonates or subcutaneous inhibitors of receptor activator of nuclear factor κB ligand (RANKL). Current clinical trials are focused on blocking the activity of kinases (SRC and cABL) and enzymes (cathepsin K) involved in osteolytic lesion progression. In contrast, few options exist for the treatment of osteosclerotic lesions - isolated lesions can be treated using palliative radiotherapy whereas multifocal lesions require systemic taxane-based chemotherapy. Pre-clinical and clinical studies have now started to address this shortfall in anti-osteosclerotic therapeutics and provide a significant focus of this chapter.
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