I have not used chemotherapy simultaneously with R-223. That combination has been studied and deemed to not be, in general, safe or more effective, so I don’t do it. But I have used enzalutamide and abiraterone, corticosteroids and antiresorptive agents such as denosumab or zoledronic acid in combination with R-223. I have not used sip-T because it is specifically indicated for minimally symptomatic or asymptomatic men, so that would be a contradiction. I have used R-223 with external beam radiation therapy (EBRT). That was allowed in the ALSYMPCA trial, and sometimes if a patient experienced disease progression with 1 focal site while on R-223, I would treat that site with EBRT and continue the R-223.

I have used abiraterone, enzalutamide, dexamethasone and EBRT in combination with R-223. I have not used chemotherapy with R-223. I do not use sip-T, bisphosphonates or RANK ligand inhibitors much, therefore I have not combined these agents with R-223.

I have not used R-223 simultaneously with any agent yet. I do not believe we have data to support its use in combination with chemotherapy or bisphosphonates. I wouldn’t exclude using it with EBRT, but I have not used it simultaneously. For instance, I have a patient who recently developed a bone fracture and an osteosynthesis who was going to receive additional radiation therapy on that osteosynthesis material. I discussed with the nuclear physician starting R-223 2 weeks after his EBRT.

Most often we hold this agent as a late drug, so often it’s used after chemotherapy. I have not used it simultaneously with chemotherapy or sip-T. Most patients have been on a bone-strengthening agent, such as denosumab or zoledronic acid. So they’ve been on it because they have bony metastatic disease. So I believe, by default, most people are on those together. I’m aware of several patients in whom it has been used with EBRT, and I don’t believe it’s been a problem for those patients.

I have used R-223 with bisphosphonates or RANK ligand inhibitors as our patients are usually already on one of those drugs. I have administered R-223 immediately after sip-T but not concurrently. I have not combined radium with chemotherapy. I may use it with abiraterone or enzalutamide in patients with disease outside of the bone. I have also used it with EBRT.

I have combined R-223 with antiresorptive agents, as patients were already on that treatment when R-223 was initiated. I also have not had a problem using it with EBRT. I have not combined it with any other treatment.

I have used R-223 with bisphosphonates and RANK ligand inhibitors. I have not used it with chemotherapy because in a Phase I trial that administered R-223 with docetaxel to patients with visceral metastases, the dose of docetaxel had to be reduced. This could compromise the efficacy of docetaxel. I have not used R-223 with EBRT, but it is something that I would consider if a patient had an isolated and painful metastasis that was not responding to therapy. Because sip-T is for patients with minimally symptomatic or asymptomatic disease, I have not used it in combination with R-223.

I have use R-223 with abiraterone, enzalutamide and other older secondary hormones. I have often used it with bisphosphonates and RANK ligand inhibitors. For patients with a high burden of metastatic disease, I use denosumab routinely with R-223. I have also combined R-223 with EBRT. I have not combined it with chemotherapy. I did use it in combination with sip-T once in a patient with slowly progressing, minimally symptomatic, bone-predominant disease.

I have routinely combined R-223 with denosumab. I have not used it in combination with chemotherapy or sip-T. I have used it sequentially with EBRT but not in combination.