Use of radionuclides in metastatic prostate cancer: pain relief and beyond.
ABSTRACT 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.
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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.Cancer Management and Research 08/2013; 5:235-42. DOI:10.2147/CMAR.S35789
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ABSTRACT: Prostate cancer is one of the most common malignancies affecting men worldwide, with bone being the most common site of metastasis in patients that progress beyond organ confinement. Bone metastases are virtually incurable and result in significant disease morbidity and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Several attractive molecules or pathways have been identified as new potential therapeutic targets for bone metastases caused by metastatic castration-resistant prostate cancer. In this review, we present the recent advances in molecular targeted therapies for prostate cancer bone metastasis focusing on therapies that target the bone cells and the bone microenvironment. The therapies covered in this review include agents that inhibit bone resorption, agents that stimulate bone formation, and agents that target the bone matrix. Suggestions to devise more effective molecular targeted therapies are proposed. Hopefully, with better understanding of the biology of the disease and the development of more robust targeted therapies, the survival and quality of life of the affected individuals could be significantly improved.Cancer Treatment Reviews 07/2014; 40(6). DOI:10.1016/j.ctrv.2014.04.003 · 6.47 Impact Factor
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ABSTRACT: Aim: Cabazitaxel is a novel taxane that is approved for use in metastatic castration-resistant prostate cancer based on the Phase III TROPIC study, which showed improved overall survival with cabazitaxel/prednisone versus mitoxantrone/prednisone. A global early-access program was initiated in order to provide early access to cabazitaxel in docetaxel-pretreated patients and to obtain real-world data. Patients & methods: We report interim safety results from an Italian prospective, single-arm, multicenter, open-label trial of 218 patients receiving cabazitaxel 25 mg/m(2) every 3 weeks plus prednisolone 10 mg/day, until disease progression, unacceptable toxicity, investigator's decision or death. Results: Patients completing treatment received a median of six cabazitaxel cycles. The most common grade 3/4 adverse events were neutropenia (33.9%), leukopenia (15.6%), anemia (6%) and asthenia (6%). No peripheral neuropathy or nail disorders were observed. Conclusion: These results confirm that cabazitaxel has a manageable safety profile in daily clinical practice and support its use in patients with prostate cancer who progress during or after a docetaxel-based therapy.Future Oncology 12/2013; DOI:10.2217/fon.13.256 · 2.61 Impact Factor