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Radium-223 as Bone-Targeted Therapy for CRPC

Insights From: Evan Yu, MD, University of Washington; Ulka Vaishampayan, MD, Barbara Ann Karmanos Cancer Institute ; Neeraj Agarwal, MD, Huntsman Cancer Institute
Published: Tuesday, Dec 11, 2018



Transcript:

Evan Yu, MD: Radium-223 is a regulatory approved agent in bone-metastatic castration-resistant prostate cancer that confers a survival benefit. It also decreases skeletal morbidity. Now, radium-223 is a very interesting compound. It’s a radiopharmaceutical. It’s in the same column of the periodic table as calcium. It interpolates into areas where there’s a lot of osteoblastic activity in bone metastases. Because it’s a radiopharmaceutical, it’s not metabolized by the liver or the kidney. It’s really degraded over time. That’s how it leads to certain adverse effects being excreted in the bowels. Diarrhea could be an adverse effect.

But the key thing that’s interesting is that it’s an alpha emitting pharmaceutical; it’s not a beta emitter. It doesn’t have as much spread, it’s very potent, and it induces double strand DNA breaks in the cancer cells after it interpolates into the bone, but it doesn’t spread all through the marrow and induce a lot of myelosuppression. That’s one of its unique characteristics. But the key issue in the ALSYMPCA trial that led to its approval was the fact that at interim analysis, there was a survival benefit. That’s really why I give the agents.

Radium-223 is an agent that I generally use for the key benefit of overall survival. External beam radiation is something that I use for patients who have symptomatic bone metastases. For instance, if they have 1 or 2 spots that are painful, they’ll gain palliative benefit. But there’s never been an overall survival benefit proven with just spot external beam radiation. Certainly, I’ll have patients with some diffused bone pain for whom I’ll use radium-223, with the idea that it may improve their bone pain. But that’s not the primary reason I’m using it. I’m using it for overall survival benefit in those patients with bone-metastatic castration-resistant prostate cancer and symptoms.

Ulka Vaishampayan, MD: The typical recommendation as you’re starting to plan for radium-223 would be to have established collaboration in advance with radiation oncology or nuclear medicine, whichever place you’re planning on collaborating with to recommend the radium-223. For the most part, if it’s radiation oncology, patients have bone pain, and they need external beam radiation to a specific area, it may be time—as they’re getting the external beam radiation—to start planning towards radium-223 therapy.

If they do not require external beam radiation therapy, then clearly the blood count assessment needs to be obtained. Patients need to have that discussion about the risk-benefit profile and efficacy with the medical oncologist. Typically, how we do it at our center is after the patient has consented to their treatment, we contact the radiation oncologist and OK the therapy. Then they take it over from there in terms of checking blood counts and administering the therapy and scheduling it.

This treatment is given once every 4 weeks for a maximum of 6 doses. You know that treatment duration and the treatment intervals need to be very clear with the patient, the medical oncologist, and the radiation oncologist. Some centers prefer to just have a 1-person coordinator. At our place, we have the medical oncologist act as the coordinator for the schedule, but that does need to be decided prior to starting the patient on therapy.

The time to treatment is not very long. I think you can plan on starting it within 1 or 2 weeks, depending on how well that collaboration is set up. Obviously, the first patient will take a little bit of time until the logistics are sorted out, but once that is done, it really runs very smoothly and there are barely any glitches once you have it figured out.

Transcript Edited for Clarity
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Transcript:

Evan Yu, MD: Radium-223 is a regulatory approved agent in bone-metastatic castration-resistant prostate cancer that confers a survival benefit. It also decreases skeletal morbidity. Now, radium-223 is a very interesting compound. It’s a radiopharmaceutical. It’s in the same column of the periodic table as calcium. It interpolates into areas where there’s a lot of osteoblastic activity in bone metastases. Because it’s a radiopharmaceutical, it’s not metabolized by the liver or the kidney. It’s really degraded over time. That’s how it leads to certain adverse effects being excreted in the bowels. Diarrhea could be an adverse effect.

But the key thing that’s interesting is that it’s an alpha emitting pharmaceutical; it’s not a beta emitter. It doesn’t have as much spread, it’s very potent, and it induces double strand DNA breaks in the cancer cells after it interpolates into the bone, but it doesn’t spread all through the marrow and induce a lot of myelosuppression. That’s one of its unique characteristics. But the key issue in the ALSYMPCA trial that led to its approval was the fact that at interim analysis, there was a survival benefit. That’s really why I give the agents.

Radium-223 is an agent that I generally use for the key benefit of overall survival. External beam radiation is something that I use for patients who have symptomatic bone metastases. For instance, if they have 1 or 2 spots that are painful, they’ll gain palliative benefit. But there’s never been an overall survival benefit proven with just spot external beam radiation. Certainly, I’ll have patients with some diffused bone pain for whom I’ll use radium-223, with the idea that it may improve their bone pain. But that’s not the primary reason I’m using it. I’m using it for overall survival benefit in those patients with bone-metastatic castration-resistant prostate cancer and symptoms.

Ulka Vaishampayan, MD: The typical recommendation as you’re starting to plan for radium-223 would be to have established collaboration in advance with radiation oncology or nuclear medicine, whichever place you’re planning on collaborating with to recommend the radium-223. For the most part, if it’s radiation oncology, patients have bone pain, and they need external beam radiation to a specific area, it may be time—as they’re getting the external beam radiation—to start planning towards radium-223 therapy.

If they do not require external beam radiation therapy, then clearly the blood count assessment needs to be obtained. Patients need to have that discussion about the risk-benefit profile and efficacy with the medical oncologist. Typically, how we do it at our center is after the patient has consented to their treatment, we contact the radiation oncologist and OK the therapy. Then they take it over from there in terms of checking blood counts and administering the therapy and scheduling it.

This treatment is given once every 4 weeks for a maximum of 6 doses. You know that treatment duration and the treatment intervals need to be very clear with the patient, the medical oncologist, and the radiation oncologist. Some centers prefer to just have a 1-person coordinator. At our place, we have the medical oncologist act as the coordinator for the schedule, but that does need to be decided prior to starting the patient on therapy.

The time to treatment is not very long. I think you can plan on starting it within 1 or 2 weeks, depending on how well that collaboration is set up. Obviously, the first patient will take a little bit of time until the logistics are sorted out, but once that is done, it really runs very smoothly and there are barely any glitches once you have it figured out.

Transcript Edited for Clarity
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