![]() ![]() The study population reflects the multimodality approach used at this point in the treatment course. Therefore, the population included a mix of prechemotherapy and postchemotherapy patients. The placebo-controlled, double-blind, prospective, randomized ALSYMPCA trial of radium-223 included more than 900 patients with CRPC who had received chemotherapy and progressed (approximately 55%) or did not receive docetaxel because they were ineligible for it or declined it (approximately 45%). They have been used for symptomatic pain control among patients with highly refractory, widespread bone metastases. Of note, neither samarium nor strontium demonstrated an overall survival benefit in a phase 3 trial. Historical radiopharmaceuticals, such as strontium and samarium, have much deeper penetration and, consequently, much higher toxicity profiles, primarily involving myelosuppression. It is therefore associated with a reduced risk of marrow toxicities, such as neutropenia or thrombocytopenia. The advantage of the larger α particle is that it has a much shallower penetration at the level of the cortical bone, and thus is less likely to penetrate the marrow and impact myeloid proliferative tissues. The earlier-generation radiopharmaceutical agents emitted β/ϒ molecules, which are, simply stated, much smaller than α molecules. NS Radium-223 is a radioisotope that emits an α molecule. More importantly, radium-223 is a life-prolongation therapy, as shown in the ALSYMPCA (Alpharadin in Symptomatic Prostate Cancer) trial, which demonstrated a statistically significant improvement for overall survival in the radium-223 treatment arm. Radium-223 (Xofigo, Bayer HealthCare) has been shown to significantly delay the development of symptomatic skeletal events. These events are not only associated with significant morbidity and quality-of-life issues, but can hasten a patient’s death. NS The past several years have seen the advent of bone-targeted therapies, such as zoledronic acid (Zometa, Novartis) and denosumab (Xgeva, Amgen), that delay the incidence of skeletal-related events (SREs), such as fracture, need for pain palliation, surgical intervention, and cord compression. H&O What are the treatment options for CRPC patients with bone metastases? Therefore, symptoms should not be the sole criteria when deciding to proceed with treatment. Oftentimes, symptoms were noticed by caregivers approximately 3 months before the patients recognized them.Īt the same time, and oftentimes counterintuitively, there are patients with large tumor burdens of bone metastases who fail to demonstrate any symptoms. The recent IPCC survey found that in approximately 50% of men, there was a 7-month delay from the time they recognized their bone symptomatology to the time they discussed it with their clinicians (including both physicians and nurses). Clearly, this symptomatology can decrease quality-of-life metrics. ![]() Patients may develop inanition, cachexia, and fatigue, which can be related to tumor burden and bone metastases. They may stop regular activities, such as walking upstairs, hitting a tennis ball, or swinging a golf club, and they may find themselves ingesting increased doses of over-the-counter analgesics, such as nonsteroidal anti-inflammatory drugs, acetaminophen, or aspirin. Their sleep pattern may be interrupted by nightly discomfort. For example, they may experience new-onset difficulties getting into and out of a car. A large survey conducted by the International Prostate Cancer Coalition (IPCC results posted at ) showed that many patients with bone metastases have symptoms they would not describe as bone-related pain. Pain is the most common symptom, and historically, the symptomatology of bone metastases was considered binary: pain or no pain. It seems likely that symptoms are more prevalent than reported. NS This question raises an important point about how to define and describe symptomatology. H&O How prevalent are symptoms in these patients? Disease often progresses despite hormonal therapy (see the figure). A study from 2010 showed that 5-year survival was 3% among prostate cancer patients with bone metastases compared with 56% in patients without bone metastases. Prognosis is significantly worse among these patients. NS Data from many phase 3 clinical trials, inclusive of both retrospective and prospective analyses, as well as prostate cancer registries from various countries, suggest that more than 90% of men who die of CRPC have bone metastases. H&O How many patients with castration-resistant prostate cancer (CRPC) develop bone metastases? Clinical Advances in Hematology & Oncology ![]()
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