Radium-223 Safety Prior to or After Chemotherapy

Daniel J. George, MD:When I treat patients with castrate-resistant prostate cancer, it almost doesn’t matter what their age is. If they’re of a good performance status, if they’re somebody who doesn’t have a comorbidity that’s life-threatening in the next 3 years, I’m going to want to offer them every treatment option that I can.

When I look at a patient and think, “I’m going to want to treat them with our secondary hormonal therapies, immunotherapy—sipuleucel-T, chemotherapy, or maybe multiple chemotherapies, and radium-223,” I need to be thinking upfront about what that sequence approach might be. If you don’t think about these things, you become reactive. When we become reactive to the disease rather than proactive, we end up delaying our treatments until it’s too late and we can’t get all of that therapy in.

So my No. 1 goal with these patients—I share this with them and make sure that this is their goal too—is to help them live for as long as possible with the best quality of life, maximizing the survival benefit of each of these treatments. The way to do that is to be proactive and keep them in a performance status of 0 or 1. Do not wait until that performance status goes down to 2. Once performance status goes down to 2 or 3, it’s difficult to benefit from any of these therapies. It’s difficult to tolerate any of them. Thinking about how I’m going to sequence these therapies and maintain that good performance status is key.

For many of our patients who have bone-only disease, starting with radium-223 has a couple of advantages. It doesn’t lower that patient’s performance status. For the most part, these patients are going to be able to tolerate that because, in a sense, it’s not systemic disease. It’s disease focused on bone. Yes, there are marrow toxicities and there may be some clearance through the gastrointestinal tract, but in general we’re not seeing other complications—cardiac complications, other muscular complications, weight loss, or other things.

It tends to have a very manageable adverse effect profile, and we see that with the adverse effect profile represented in the ALSYMPCA study. Even the marrow toxicity tends to be really mild in those early circumstances, so I’d like to offer that to my patients when appropriate. I know I can give docetaxel chemotherapy afterwards. I know I can give cabazitaxel chemotherapy after that.

I’m going to want to do those therapies in sequence as well. For our patients who present with metastatic disease upfront, we sometimes offer docetaxel in that hormone-sensitive metastatic setting. Using radium-223 in the castrate-resistant prostate cancer setting offers a different mechanism of action. There are patients who present with visceral disease for which radium-223 is not going to be appropriate, and that’s OK. This isn’t for every patient, but for at least 50% or more of our patients with bone-dominant disease, it makes sense to think about using this agent. I can use it after docetaxel, but, in many cases, performance status-wise, it’s best tolerated when it’s given pre-chemotherapy.

Transcript edited for clarity.

mCRPC Treated With Radium-223 Therapy

January 2015

H&P:

• A 71-year old gentleman presented with urinary incontinence
• Past medical history: HBP controlled with lisinopril
• On digital rectal examination prostate was enlarged
• Patient was asymptomatic

Imaging:

• Transrectal ultrasound and biopsy revealed adenocarcinoma of the prostate gland with a Gleason score 9 [4+5] with 9 of 12 cores positive
  • PSA, 10.2 ng/mL
• CT scan was negative for metastases
• He was started on a 3-month depot injection of leuprolide 22.5 mg and treated with 7800 cGy IMRT

April 2016

• Patient returned for 3-month injection; his PSA level increased to 47 ng/mL
  • CT/Bone scans were negative for metastases
• He was started on enzalutamide
  • PSA, 12 ng/mL

October 2016

• 6 months later the patient complained of severe fatigue and lower back pain
  • Imaging with CT and bone scan showed multiple metastases of the spine and pelvis
  • PSA levels increased to 76 ng/mL
  • ALP, 268 U/I
• Radium-223 therapy was initiated in addition to continuing enzalutamide
• After 3 infusions of radium-223
  • PSA declined to 31 ng/mL
  • ALP decreased to 80 U/l
  • CT scan showed no new bone metastases
  • Fatigue decreased, and patient’s physical activity increased