Radium-223 Administration for mCRPC

Glen Gejerman, MD:The ALSYMPCA trial was a very important trial. It showed that for patients who have progressive metastatic castrate-resistant prostate cancer, the administration of radium-223—what we call Xofigo—has several very important milestones. Number 1, it alleviated pain in about half of the men. Number 2, it prevented a secondary skeletal event. The most important finding in that study was that there was a survival benefit. Now, we know that there’s a concept called therapeutic layering. You don’t want to start and stop one treatment after another. There are synergies between the treatments, so it’s quite logical to add these drugs—abiraterone as well as radium-223—when patients have symptomatic bony disease and are castrate resistant.

I think it’s extremely important that we find patients who are eligible for radium-223 early on. We know that in the ALSYMPCA trial, only about 70% of patients received the full 6 cycles, and we know that patients who received 5 to 6 cycles as opposed to 1 to 2 did much better. When patients are heavily pretreated, be it with chemotherapy or other modalities, they are less likely to have the bone marrow reserve that they need to complete 6 cycles of radium-223. So, finding these patients early on, as soon as they have multiple sites of disease or even when there are early symptoms, such as fatigue or difficulty in mobility, not necessarily even pain—it’s important to initiate the drug at that point so you can ensure that patients receive the full 6 cycles and gain the maximum benefit. If we can identify patients early on, especially as we begin to layer in additional therapies such as abiraterone or enzalutamide, the likelihood that those patients will gain the maximum benefit will increase.

The important thing is that we have to work in a multimodality fashion. So, we have to work with our medical oncology colleagues and our urology colleagues to make sure that we identify patients early on. And we’re all beginning to understand how to use what I would call almost an embarrassment of riches. We have so many different drugs that we can use, and it’s very important that we identify which patients should receive a drug at certain points. Patients who have high volume bulky disease, large lymph nodes, or visceral involvement certainly should receive chemotherapy. But, if a patient is early on in their castrate-resistant phase and they have bony disease, those are the patients who should receive radium-223. A good relationship with a medical oncologist is critical, so that we can agree which patients should receive the various modalities.

Radium-223 is approved for patients who have castrate-resistant metastatic disease, but you also have to have symptoms. It’s very important to sort out what symptoms are in prostate cancer. They’re not only in patients who have significant pain. They could also be fatigue or difficultly with mobility. It’s very important to spend time with a patient and really clarify if they’re at the point where they’re symptomatic enough that radium-223 should be initiated.

Once a patient is seen to have castrate resistance, which means they’re no longer responding to the initial Eligard or Lupron [leuprolide] and their PSA is rising, that’s a good time to initiate the secondary androgen receptor medications. It could be abiraterone or enzalutamide. But, for a patient who has symptoms with their bony metastatic disease, that’s when radium-223 should be added into the mix.

One of the important parts of this treatment that’s important to discuss with the patient is that their PSA may not drop. So, when you’re delivering radium-223, we don’t use PSA as a marker. Instead, we use alkaline phosphatase, which is a surrogate of bone metabolism. Very often, these patients have spent the last 5 to 10 years constantly looking at that PSA number. We do not expect that it’s going to drop. In fact, it may rise, unless we’re using another drug such as abiraterone. But with the alkaline phosphatase, as that drops from month to month, patients are often very reassured.

When we identify patients early on, patients who have not been heavily pretreated with chemotherapy, those patients tend to tolerate radium-223 the best. They’ve got more bone marrow reserve. There’s certainly less anemia and thrombocytopenia, as was found in the ALSYMPCA trial. So, it’s very important to work with our colleagues to identify these patients early on. For those patients who complete the full 6 cycles, they generally do extremely well.

Because radium-223 is an alpha emitter, it has a very short action, so you don’t have to worry about radiation protection other than using gloves. For example, I tell my staff who are administering it, “If there’s ever going to be a spill, you take a piece of paper and put it on top of it.” The range of the exposure is 2 to 10 cell diameters, so it’s very, very safe. In terms of patients, as long as they practice good bathroom hygiene, there are no precautions once they go home.

Transcript edited for clarity.

December 2012

• A 65-year old gentleman presented to a urologist with urinary incontinence
• Digital rectal examination was unremarkable
• Serum prostate-specific antigen (PSA) level of 10.8 ng/mL
• Transrectal ultrasound and biopsy revealed adenocarcinoma of the prostate gland with Gleason score 7(3 + 4)
• Bone scan and CT showed no evidence of metastasis
• The patient opted for radical prostatectomy; pathology confirmed Gleason 7 prostate cancer with evidence of extracapsular extension and negative nodes; pT3aN0
• Immediately following surgery, his PSA level was undetectable (<0.1 ng/mL)

December 2014

• Two years later the patient developed disease progression
  • PSA level increased rapidly to 15 ng/mL
  • He was asymptomatic
• He was referred to an oncologist by his urologist
• Bone scan and CT were negative
• He was started on androgen deprivation therapy and had an initial response of PSA decline to 0.5 ng/mL

December 2015

• Over the next year, his PSA level increased to 35 ng/mL
• Repeat imaging studies were done:
  • Bone scan showed multiple boney metastases in the spine, pelvis, ribs, and femur
  • CT scan showed no visceral or nodal disease
• Within 3 months his PSA level rose to 145 ng/dL and he began complaining of fatigue and pain
• He was started on abiraterone and prednisone
• Additionally, he opted for therapy with radium-223
• After 3 infusions of radium-223 his PSA declined to <10 ng/dL; ALP remained stable
• After 6 cycles of treatment, CT and bone scan confirmed stable disease with no new metastases
• The combination was generally well tolerated; the patient experienced grade 2 anemia and fatigue