Prostate cancer is the most common malignancy in men. Over the past 10 years, a number of drugs have been approved for the treatment of prostate cancer. One of these drugs, Radium 223 dichloride (Xofigo), is a radioisotope that causes irreversible DNA double-strand breaks in cells, thereby inducing tumor cell death. Radium 223 can mimic calcium and specifically target skeletal lesions for therapeutic effect.
Radium 223 has been approved in the United States and Europe for the treatment of castration-resistant prostate cancer (CRPC) that has not yet developed visceral metastases but has significant bone metastases.
What is radium 223?
Radium 223 is a mildly radioactive form of metallic radium. It was once known as Alpharadin and is now known by the trade name Xofigo.
Clinicians often use radium 223 to treat prostate cancer that has developed bone metastases. Radium 223 can be a good treatment for multiple tumors in the bone, and it can kill cancer cells in these areas and reduce the pain associated with the cancer.
Patients need to go to a specific hospital to receive radium 223 because only some hospitals are able to offer this treatment.
What is the mechanism of action of radium 223?
Radium and calcium have similar biology. Like calcium, radium is absorbed by active bone cells, a feature that makes it a good way to specifically target cancer cells in the bone area. Cancer cells are more active than normal bone cells and are therefore more likely to ingest radium 223.
Radium 223 produces radiation when it enters bone cells, and the rays penetrate over a very short distance, only about 2 to 10 cells, which is shorter than 1 millimeter. This means that cancer cells are exposed to high doses of radiation and eventually die, while healthy cells are only exposed to lower doses of radiation, if at all. As a result, this therapy minimizes damage to surrounding tissue with minimal side effects.
How effective is radium 223?
The approval of radium 223 was based primarily on data from the pivotal phase III ALSYMPCA study. This randomized controlled trial enrolled 921 patients with destructive-resistant prostate cancer with symptomatic bone metastases and compared the efficacy of radium 223 to placebo.
The results showed that patients treated with radium 223 had a significantly longer overall survival time of 14.9 months compared with 11.3 months for patients treated with placebo. There was also a significant delay in the time to skeletal symptoms in patients treated with radium 223 compared with the placebo group (15.6 months versus 9.8 months, respectively).
In addition, the biological response (prostate-specific antigen and serum alkaline phosphatase levels) was improved in the radium 223-treated group compared with the placebo group.
Also, radium 223 treatment was well tolerated, with no significant difference in the incidence of grade 3 and 4 adverse events between the two groups. The most common adverse reactions included anemia, thrombocytopenia, and diarrhea.
How was radium 223 treatment administered?
During each treatment, the doctor injects radium 223 into a vein in the patient’s upper extremity through a short, thin catheter. Usually, the injection takes about 1 minute.
The frequency of injections is typically repeated every 4 weeks, and the patient will receive a total of about 6 treatments. After the outpatient radium 223 injection, the patient can go home without being hospitalized.
What should I expect after radium 223 treatment?
Patients receive radium 223 as an outpatient.
Patients will have radioactive material in their urine for a few hours after radium 223 treatment and in their stool for up to 7 days after treatment. However, there is no need to worry because the total amount of radiation is very small and will diminish over time.
The following precautions usually need to be followed after treatment:
- Drink plenty of water for a few days after treatment.
- Pissing should be done sitting on the toilet and not standing or using the urinal for the first few days.
- Try to wash your hands well after each visit to the toilet.
- For 7 days after receiving Radium 223, wipe carefully after each bowel movement (it is recommended that patients preferably wear gloves).
- For 7 days after radium 223 treatment, the toilet should be flushed twice after each toilet break.
- If the patient shares the toilet, wipe the toilet seat after using the toilet.
- If the patient’s clothes are soiled with urine or feces, they should be washed separately.
After radium 223 treatment, male patients should use contraception for 6 months, as this treatment can cause sperm damage. Prior to treatment, patients should consult with their healthcare provider about effective birth control methods.
If the patient plans to have children in the future, sperm storage should be considered prior to treatment, which can be done in consultation with the clinician.
What are the possible side effects of radium 223?
Side effects of radium 223 include diarrhea and nausea, but these symptoms are generally mild.
This treatment can sometimes cause a decrease in blood cells after a few weeks, which may increase the risk of infection, anemia, and local bruising. Therefore, patients need to have regular blood tests after treatment.
Very few patients experience increased pain at the site of the bone tumor for a few days or weeks after treatment. Once this occurs, patients should notify their doctor or nurse and take the relevant pain medication.
Summary
Radium 223 is the first drug in its class to show significant efficacy in metastatic desmoresistant prostate cancer. Radium 223, along with novel hormone therapies and chemotherapy, offers additional treatment options for this disease. And because of its relatively weak toxic effects, it is expected to be the best option for those with bone metastases (no visceral metastases) who are not candidates for docetaxel therapy.
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