Radium-223 or Xofigo was first approved in 2013 as “an alpha particle-emitting radioactive therapeutic agent indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.” That meant (and still means) one course of treatment with six cycles of radium-223. However, …
There have for some considerable time been reasons to believe that it is possible to give more than one course of treatment with radium-223 to men with metastatic, castration-resistant prostate cancer (mCRPC), and a paper just published by Sartor et al. in Annals of Oncology now seems to confirm this belief based on data from a cohort of 44 patients with mCRPC that had metastasized to bone, who had been treated with a single, initial course of six injections of radium-223 with no on-treatment bone progression, but who all had subsequent radiologic or clinical progression.
Sartor et al. carried out an international, prospective, Phase I/II clinical trial that enrolled these 44 patients. The primary endpoint of the trial was safety; additional exploratory endpoints included time to radiographic bone progression, time to total alkaline phosphatase and PSA progression, radiographic progression-free survival, overall survival, time to first symptomatic skeletal event (SSE), SSE-free survival, and time to pain progression.
Decisions about the use of concomitant therapeutic agents (e.g., agents to treat breakthrough pain; LHRH agonists; antiandrogens; and others) were allowed at the discretion of the investigators, with the exception of chemotherapy and initiation of new abiraterone or enzalutamide.
Here are the core results of the study:
- 29/44 patients, (66 percent) received all six re-treatment injections.
- Median time from the prior completion of the patients’ initial radium-223 treatment was 6 months.
- 41/44 patients (93 percent) reported one or more treatment-emergent adverse events.
- There were no Grade 4/5 hematologic treatment-emergent adverse events.
- 1/44 patients (2 percent) exhibited radiographic bone progression while on treatment.
- 8/44 patients (18 percent) had radiographic soft tissue tumor progression while on treatment (three lymph node metastases and five visceral metastases).
- Median times to biochemical progression were
- 2.2 months based on PSA progression
- Not reached based on total alkaline phosphatase progression
- Median radiographic progression-free survival was 9.9 months (with a 12.8-month maximum follow-up).
- 5/44 patients (11 percent) died.
- 8/44 patients (18 percent) experienced first SSEs.
- Median overall survival, time to first SSE, and SSE-free survival were not reached.
- 5/36 evaluable patients (14 percent) had pain progression (based on a baseline worst pain score ≤ 7).
- After 2 years of follow-up, 28/44 patients (64 percent) patients died, and the median overall survival was 24.4 months.
Re-treatment with a second course of six radium-223 injections after disease progression is well tolerated, with minimal hematologic toxicity and low radiographic bone progression rates in this small study with limited follow-up. Favorable safety and early effects on disease progression indicate that radium-223 re-treatment is feasible and warrants further evaluation in larger prospective trials.
Obviously, one would prefer to find other forms of treatment for men with mCRPC who had already progressed on radium-223 — forms of treatmen t that could both relieve that bone pain and extend their lives with limited risk for complications and side effects. While we are hunting for such forms of treatment, however, we still need to be able to offer appropriate therapy for men progressing after a first course of treatment on radium-223.
Based on this study, we would hope that Bayer would consider a larger trial of repeated radium-223 treatment among men who had already progressed on a first cycle of radium-223. The goal should be to seek approval of such repeated treatment in order to palliate patients’ bone pain and help to maintain their quality of life.
Filed under: Drugs in development, Living with Prostate Cancer, Management, Treatment | Tagged: radium-223, repeat, Treatment, Xofigo |
THE "NEW" PROSTATE CANCER INFOLINK 
I have had one metastasis for the last 10 years, and now that my PSA has gone over 100 the doctor is fast moving me to do radium-223. I have no pain, nor have I ever had pain in my bones. I’m afraid that if I take the radium-223 it will speed up my death.
Dear Joseph:
So an important question is how have you been being treated to date? For example:
— Has your PSA reached 100 ng/ml while you have been being treated with some type of androgen deprivation therapy (ADT; also known as hormone therapy), such as Lupron or similar?
— Have you ever had chemotherapy (with a drug like docetaxel/Taxotere)?
— Have you ever had treatment with drugs like enzalutamide (Xtandi) or abiraterone acetate (Zytiga)?
As far as I am aware, there is no good reason to believe that a drug like radium-223 (Xofigo) would “speed up your death”. In clinical trials this drug actually increased the survival time (on average) of the patients who were treated with it — albeit only by a few months.
I had abiraterone for about 2 years; I had nine treatments of Taxotere in 2009 which left me with no hair on my body except my head. I had enzalutamide for about 6 months, and was taken off when my PSA went over 100 3 months ago.I have had Zytiga before, and they just started me back on Zometa 2 months ago. I go to the VA, but the doctors are from the University of California, Davis. Now they are telling me that they should never have taken me off the Zometa. I have an appointment every 3 months. I’m loaded with cancer spots on my ribs (9), spine, left leg, both shoulder, hip, and like I said never any pain. Tomorrow I start radium-223.
Dear Joseph:
Thank you for the additional information. That is very helpful. And I have no idea why they would have taken you off the Zometa either.
My assumption would be that the goal of trying the radium-223 (Xofigo) is try try to get your PSA level back under control. It clearly isn’t to control bone pain since you don’t have any of that.
I would repeat my comment that I don’t know of any good reason to believe that a treatment like this would shorten your life span. And if it could drop your PSA back down to a lower level for a period of time, it may actually help to extend your life span over time.
Well, I’ll keep you posted on what does, or doesn’t happen. Thank you.