Patients must have bone-predominant disease without visceral disease. They must be symptomatic, and the level of pain can be reasonable. It doesn’t have to be pain requiring opiates but symptoms requiring treatment. Fatigue is another common symptom that could be related to bone disease. Those would be the 2 most common symptoms I would consider. In terms of lymph node metastases, if it’s not a bulky lymph node metastasis, then I would feel fine using R-223.

In the Phase III trial the reduction of bone pain from R-223 was not rigorously addressed, but from my own experience I believe R-223 does reduce bone pain in some men but not all. It can actually lead to some flares in bone pain for a week or two. But pain tends to improve over the first 1 to 2 months, and for some patients I have been able to reduce the dose of narcotics to a low level. They’re usually not rendered asymptomatic, though.

I typically don’t offer R-223 to patients who have any disease outside of the bone unless they have small nodal metastases, less than 3 centimeters, in the pelvis.

In my practice, many patients on R-223 have experienced relief of bone pain, and it can be significant.

I would offer it to patients if I have no alternative treatment options and to patients who have either pain or extensive bone disease with a significant risk of skeletal-related events. If the patient had 99% predominant bone disease and 1 positive lymph node, I would not be concerned about using R-223 in that patient. If the patient had liver metastases, I would not use R-223.

I have treated a limited number of patients, and from that narrow experience I would not say that R-223 relieves bone pain. I have had one patient experience mild improvement in bone pain, but he is still receiving opiates.

We tend to use R-223 for patients with more extensive symptomatic bony metastatic disease in the absence of any visceral disease. We tend to follow the label and avoid it in those patients who have any evidence of visceral disease. That is the way the ALSYMPCA trial was designed. That doesn’t necessarily mean there’s not utility, but we tend to stick with the label.

I know that R-223 can lead to relief in bone pain, and this is an important quality-of-life issue. I know that it has helped. It does not happen in every patient, but it has happened in a good majority, who experience a reduction in their requirements for pain medication.

I follow the label, so I use R-223 for patients with metastatic castration-resistant disease. I reserve R-223 for patients who have more bony metastases. For patients with 1 or 2 metastases, I might not use radium at that point even if they are symptomatic. I do use R-223 in patients who have other sites of disease, such as nodal or even visceral disease, as long as I’m combining it with another agent. I do not use it in patients who are asymptomatic, but I don’t want to wait until they are extremely symptomatic, either.

I believe R-223 relieves bone pain, but also we can be fooled by the pain flare. I also believe that understanding of the ALSYMPCA trial is not good: The study randomly assigned patients to best supportive care with or without radium. Best supportive care could have included radiating a site of fairly significant pain, and that may contribute to relief of bone pain. I was a little disappointed that R-223 didn’t cause more rapid pain relief in some patients. In fact, some patients got worse before they got better. We often tell patients that the pain may not be relieved immediately, until after the second, third or fourth infusion.

In my hospital we have a team of people who look over the indications and make sure that the patient fulfills the label requirements. I wouldn’t administer treatment to asymptomatic patients, but if they were having a little bit of bony discomfort and not taking narcotics, I would consider it for patients with only minimal complaints.

R-223 can relieve bone pain, but its effect is not consistent from patient to patient, neither is the extent of relief. It is highly variable and I can’t predict who would benefit in this regard.

I don’t use R-223 for patients with visceral metastases to avoid compromising the effectiveness of any treatment of the visceral metastases with agents such as docetaxel. That can be fatal.

In my experience, R-223 can result in a significant reduction in bone pain for some patients.

I administer R-223 for patients with bone-dominant disease. I don’t have any problem administering it to patients who are asymptomatic. In the ALSYMPCA trial, patients had to be symptomatic. If you took 1 acetaminophen tablet a day, you were considered symptomatic. Approximately 43% of the people on the study were not taking opiates, and it didn’t make any difference in terms of how patients fared, except that patients on non-narcotics lived longer. However, the hazard ratio between the group treated with radium and the untreated arm was essentially the same. So I am personally not convinced that you must have painful bone lesions before you’re a candidate for R-223.

In terms of lesions outside the bone, in the ALSYMPCA trial patients were excluded if they had visceral metastases or malignant lymphadenopathy larger than 3 centimeters in the short-axis diameter. I obtain CAT scans and bone scans on all my patients. Bone scans give me an idea about the osteoblastic disease, and CAT scans give me an idea about soft tissue disease. I’ve administered R-223 to patients with small pulmonary lesions.

I make a calculation as to how good bone-targeted therapy is going to be for this patient. If the patient has bone-dominant disease, then I’m more likely to think about bone-targeted therapy in combination with hormones. But if I have a patient with involvement of 59 lymph nodes and 3 bone metastases, I’m probably not considering R-223 for that patient.

I’m not sure if R-223 results in a dramatic improvement in bone pain because I use it in combination with other agents. If you go to the literature, you can dig up data suggesting that it results in some bone relief, but these data are not from optimally controlled trials. I believe that the randomized, controlled trial produced some indications, for instance, less use of radiation therapy to bone. The best evidence to me is that radiation to bone as a secondary endpoint was significantly reduced in the R-223 arm compared to the placebo arm in the ALSYMPCA trial.

I believe it’s ideally suited for patients who have 6 or more symptomatic bone lesions and who clearly have CRPC. By “symptomatic” I mean that they’re taking any form of an analgesic for the cancer-related bone pain. I have started to aggressively have the conversation with these patients as early as possible, because I want them to be able to receive their full course of therapy, which is once every 4 weeks for 6 cycles.

If you review the ALSYMPCA data, patients were eligible for inclusion with soft tissue or lymph node enlargement up to 3 centimeters. The only exclusion was visceral metastases, so I would consider R-223 for patients with disease outside the bone.

I have had patients on R-223 who have decreased their narcotic analgesic requirement for bone pain. I’ve seen patients improve their performance status, mainly as manifested by their ability to ambulate.