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.
"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 "
[Show abstract][Hide abstract] 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(1):235-42. DOI:10.2147/CMAR.S35789
[Show abstract][Hide abstract] ABSTRACT: The treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) has significantly changed in the recent years. We provide an updated summary of the new therapeutic agents in this disease and discuss open questions and future challenges.
mCRPC is now known to frequently retain sensitivity to hormonal manipulation even after the development of castration resistance, and both the androgen synthesis inhibitor abiraterone and the androgen-receptor antagonist enzalutamide have recently shown to prolong survival in mCRPC patients after chemotherapy. Cabazitaxel, a new-generation antitubulin chemotherapeutic, and the radionuclide radium-223 chloride have also been shown to prolong survival. The biological agent cabozantinib, an orally bioavailable tyrosine kinase inhibitor with activity against Met and vascular endothelial growth factor receptor 2, demonstrated promising results in a phase II trial and is currently being assessed in two large randomized phase 3 controlled trials.
This recent progress is unprecedented and has already translated to a significant increase in the available armamentarium of drugs for mCRPC. Nonetheless, there are still significant unresolved questions as to the proper sequencing of these novel drugs along the disease continuum. Moreover, the problem of drug resistance, either primary of acquired, continues to be a major therapeutic obstacle.
Current opinion in supportive and palliative care 06/2013; 7(3). DOI:10.1097/SPC.0b013e328362ffef · 1.66 Impact Factor
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