How Should I Use This Medicine
This medicine is for injection into a vein. It is given by a health care professional in a hospital or clinic setting.
Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.
Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.
Ra Mechanism Of Action
223Ra is a radioactive isotope that decays to stable lead after a complex disintegration path with several radioactive daughters that produce four alpha particles . 223Ra decay chain is as follows: 223Ra 219Rn 215Po 211Pb 211Bi 207Tl 207Pb . 223Ra can be produced quite easily and in high amount from elution of an actinium-227/thorium-227 generator system . 223Ra physical half-life of 11.4 days allows long-distance shipment., The average particle energy per decay of 223Ra is 5.7 MeV. The combined energy for the complete decay chain of 223Ra including daughter radionuclides is 28.2 MeV. This is much higher than that of beta-emitter bone-targeting radiopharmaceuticals, such as 89SrCl2 and 153Sm-EDTMP, with, respectively, 0.58 and 0.22 MeV. Gamma particles are also emitted during 223Ra disintegration, allowing scintigraphy imaging . After intravenous injection, 223Ra acts as a calcium analog and about 25% is taken up by bone. It concentrates in sites of active mineralization with high osteoblastic activity .24 223Ra is mainly excreted by the gastrointestinal tract, and < 1% of the injected activity remains in the blood 24 hours after injection. Bone endosteum is the organ with the highest dose after 223Ra injection at therapeutic dose , and the corresponding absorbed dose to the red bone marrow is 1.6 Gy. No significant redistribution of 223Ra radioactive daughters has been observed in preclinical and clinical studies.
223Ra mechanism of action in bone metastases.
Snmmi 201: Current And Future Role Of Radium 223 In Prostate Cancer
Phillip Koo, MD,Gandaglia G, Karakiewicz PI, Briganti A, et al. Impact of the Site of Metastases on Survival in Patients with Metastatic Prostate Cancer. European urology 2015 68: 325-34. Suominen MI, Fagerlund KM, Rissanen JP, et al. Radium-223 Inhibits Osseous Prostate Cancer Growth by Dual Targeting of Cancer Cells and Bone Microenvironment in Mouse Models. Clinical cancer research : an official journal of the American Association for Cancer Research 2017 23: 4335-46. Smith M, Parker C, Saad F, et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases : a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology 2019 20: 408-19.
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Clinical Trials Of Radium 223 Dichloride
The FDA approval for Xofigo was based on the results of a Phase III clinical study known as ALSYMPCA . It was a randomised, double-blind, placebo controlled study. It enrolled 921 patients at more than 100 centres across 19 countries. The patients enrolled had castration-resistant prostate cancer with symptomatic bone metastases.
The patients were administered with Xofigo 50 kBq /kg intravenously every four weeks for six cycles with best standard of care, or best standard of care plus matching placebo. The primary efficacy endpoint of the study was overall survival . The secondary endpoints included finding time to first symptomatic skeletal event according to the external beam radiation therapy .
The results of the interim analysis showed that the patients administered with Xofigo plus best standard of care showed statistically significant improvement when compared to the patients receiving placebo plus best standard of care. The median overall survival in Xofigo plus best standard of care group was 14 months compared to 11.2 months in placebo plus best standard of care. The interim analysis also found that the patients treated with Xofigo showed a delay in time to first symptomatic skeletal event , compared to placebo.
An updated analysis was conducted after the study, which found the median OS to be 14.9 months in Xofigo patients compared to 11.3 months in placebo group.
Discussions With The Patient And Their Caregiver At The Start Of Radium
The healthcare provider has a responsibility to explain to the patient and their caregiver all of the approved options that are available to treat mCRPC, the rationale for selecting radium-223, and what the patient might expect during treatment . The patient should also be made aware that they may eventually receive all other available therapies as needed to control their disease and increase survival over the course of treatment whether in combination or sequentially , depending on drug availability and reimbursement limitations. As part of this discussion, it should be noted that although there are no contraindications for concomitant administration of radium-223 with other approved CRPC therapies , the concomitant administration of chemotherapy or other systemic radioisotopes with radium-223 is contraindicated owing to concerns of myelosuppression .
Table 3 Key elements for patient education
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The Potential Of Radium
The majority of patients with metastatic castration-resistant prostate cancer have evidence of bone metastases. Among available bone-targeted therapies, only radium-223 dichloride , a targeted alpha emitter that binds to areas of increased bone turnover in metastases, has been shown to improve survival rates.
The phase 3 ALSYMPCA trial showed that radium-223 increased overall survival by more 3 months compared with placebo among patients with metastatic CRPC and bone metastases .1 Based on these results, the US Food and Drug Administration approved radium-223 in 2013 for patients with CRPC, symptomatic bone metastases, and no known visceral metastatic disease.
Yet according to Oliver Sartor, MD, medical director of Tulane Cancer Center in New Orleans, Louisiana, there is some controversy about which patients would benefit most from the use of radium-223 in todays treatment landscape.
Radium-223 was developed in the context of older therapies that are not commonly used today, Dr Sartor explained. The current FDA approvals include agents such as abiraterone and enzalutamide, but in the ALSYMPCA trial there was no utilization of these agents.
How Radium 223 Dichloride Works
There are two different types of radiation therapy, which are known as external beam radiation and brachytherapy . Radium 223 dichloride is a mildly radioactive form of the metal radium and it is one of the drugs used in brachytherapy. A radiopharmaceutical composed of the dichloride salt of the alpha-emitting isotope radium Ra 223, with antineoplastic activity, defines the NCI Drug Dictionary. Like calcium, radium targets bone tissue and preferentially accumulates in osteoblastic lesions, such as those seen in areas of bone metastases. Radium Ra 223 forms complexes with hydroxyapatite and becomes incorporated into the bone matrix. The radioisotope Ra 223 kills bone cancer cells through local emission of high energy alpha particles, causing DNA double-strand breaks and tumor regression in the skeleton. The short range effects of alpha emission allows for localized DNA damage with limited toxicity to nearby healthy bone tissue.
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What Does This Mean For Me
Bone loss and fracture are well-known side effects of treatment for metastatic prostate cancer. If you are receiving androgen deprivation therapy with or without Radium-223 for treatment of mCRPC, you might want to ask your doctor about your risk of bone fracture while taking these medications and whether adding a BPA may be beneficial.
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What Is Radium 223
Radium 223 is a mildly radioactive form of the metal radium. It used to be called Alpharadin and now has the brand name Xofigo .
Radium 223 can shrink areas of cancer cells that have spread to the bone. This reduces symptoms, such as pain, and helps you feel more comfortable.
You might need to travel to a different hospital for the treatment because it isnt available in every hospital.
Radium 223 is for people with prostate cancer who:
- had hormone treatment that is no longer working
- have either had or aren’t suitable for docetaxel
- have cancer that has spread to bones but not other organs
- are not having treatment with abiraterone
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Radium 223 Dichloride To Treat Prostate Cancer
On May 15, 2013, the Food and Drug Administration approved radium 223 dichloride for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease, stated the National Cancer Institute. Radium 223 dichloride, also known as Radium Ra 223 dichloride, is an alpha-particle emitting radiotherapeutic drug that mimics calcium and forms complexes with hydroxyapatite at areas of increased bone turnover, such as bone metastases. The FDA also defines as a recommended dose and schedule 50 kBq/kg radium 223 dichloride, slowly and intravenously administered, over a minute every four weeks for six cycles.
Note: Prostate Cancer News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
After Radium 223 Treatment
After the treatment, some radiation may be present in your urine and in your poo for 1 week. The total amount is extremely small and gets lower each day.
The team looking after your treatment usually ask you to take the following precautions:
- Drink plenty of fluids for a few days.
- Sit down on the toilet when passing urine, instead of standing up or using a urinal for the first few days.
- Wash your hands thoroughly every time you use the toilet.
- Wipe yourself very carefully after having your bowels open .
- Flush the toilet twice after using it.
- Wipe the toilet seat after using it if you share the toilet with other people.
- Wash clothing separately if it becomes soiled with urine or faeces.
After this treatment, men shouldn’t father a baby for at least 6 months because the treatment can cause sperm damage. Talk to your doctor or nurse about effective contraception, such as condoms before having the treatment.
It might be possible to store sperm before the treatment if you are planning to have children in the future.
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How Does Radiotherapy Treat Advanced Prostate Cancer
Radiotherapy can be used in different ways to treat advanced prostate cancer:
- As part of your first treatment for advanced prostate cancer If youre offered radiotherapy as part of your first treatment, youll have a type called external beam radiotherapy.
- To improve symptoms in areas where the cancer has spread You may have external beam radiotherapy to the part of the body where the cancer is causing problems.
- To help some men with bone pain live longer If your cancer is causing bone pain, you may be offered a type of internal radiotherapy called radium-223 to help you live longer and to treat the bone pain.
A clinical oncologist or radiographer will plan your radiotherapy with you. They will explain which type of radiotherapy you will have, how long the treatment could take and the possible side effects. This could depend on where your cancer has spread to, any symptoms youre having, and your general health and fitness.
A team of treatment radiographers will give you the treatment. They’ll also give you support and information during your treatment.
The information on this page is for men with advanced prostate cancer. If your cancer hasn’t spread to other parts of the body, read our information on external beam radiotherapy for localised or locally advanced prostate cancer instead.
Overview Of Clinical Trial Data
Table 2 Key efficacy and safety data for radium-223 from phase 3 trialFig. 1: Prospective subgroup analysis of hazard ratios for death in the radium-223 ALSYMPCA trial
The Eastern Cooperative Oncology Group scores the performance status of patients with respect to activities of daily living as follows: 0, fully active and able to carry out all predisease activities without restriction 1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light nature 2, ambulatory and up and about for more than 50% of waking hours and capable of self-care but unable to carry out work activities 3, capable of only limited self-care and confined to a bed or chair for more than 50% of waking hours 4, completely disabled and 5, dead. The category for use of opioids includes patients with a score of 2 or 3 on the World Health Organization âladderâ for cancer pain . The category for non-use of opioids includes patients without pain or opioid use at baseline and patients with a score of 1 on the WHO ladder for cancer pain. Superscan refers to a bone scan showing diffuse, intense skeletal uptake of the tracer without renal and background activity. ALP denotes alkaline phosphatase, and NE not evaluated. Reproduced with permission from Parker et al.
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Zytiga Treatment Of Metastatic Castration
Developed by Coughar Biotechnology, abiraterone acetate was discovered by the UK Institute for Cancer Research.
Bayer entered into an agreement with Algeta for the development and commercialisation of Xofigo, in September 2009. As per the agreement, Bayer has the right to develop and apply for the health authority approvals across the world, and commercialise the drug internationally.
Bayer has begun the commercial production of Xofigo and the drug is expected to enter the US market shortly. The drug will be co-promoted in the US by Algeta US. Bayer also holds the international marketing rights of Xofigo.
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What Side Effects May I Notice From Receiving This Medicine
Side effects that you should report to your doctor or health care professional as soon as possible:
- allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
- low blood counts – this medicine may decrease the number of white blood cells, red blood cells and platelets. You may be at increased risk for infections and bleeding
- pain, redness, or irritation at site where injected
- signs of infection – fever or chills, cough, sore throat, pain or difficulty passing urine
- signs of decreased platelets or bleeding – bruising, pinpoint red spots on the skin, black, tarry stools, blood in the urine
- signs of decreased red blood cells – unusually weak or tired, feeling faint or lightheaded, falls
- signs of infection – fever or chills, cough, sore throat, pain or trouble passing urine
- swelling of the ankle, feet, hands
Side effects that usually do not require medical attention :
- dry mouth
- nausea, vomiting
This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
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What Happens After Radiotherapy
After you finish your radiotherapy, you will have regular appointments to check how well your treatment is working and monitor any side effects. Your doctor or nurse will let you know how often youll have appointments.
You will have regular blood tests to measure your level of PSA . Your doctor will also ask you about any side effects from your treatment and any symptoms you might have.
If youve had external beam radiotherapy to treat bone pain, you may find the pain gets worse during treatment and for a few days afterwards this is called a pain flare. Your doctor might prescribe some pain-relieving drugs to help with the pain, or increase the dose that you already take.
You should notice that the pain gradually improves, though it might take a few weeks for the treatment to be most effective. The pain relief usually lasts for several months and you may be able to reduce the dose of any pain-relieving drugs you are taking. But speak to your hospital team or GP first you shouldnt reduce the dose suddenly. If your pain or other symptoms dont improve, talk to your doctor, radiographer or nurse.
If your pain comes back, they might suggest another course of radiotherapy. If youve already had external beam radiotherapy to one area, you may be able to have it again to the same area. This will depend on the dose youve already had. If you have bone pain in more than one new area, you might be able to have more external beam radiotherapy or a course of radium-223.
What May Interact With This Medicine
Interactions have not been studied.
This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.
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About Dr Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
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Study Design And Treatment
Study design and patient inclusion and exclusion criteria for this phase 3b study have been previously reported in detail . Patients were18years or older, had histologically or cytologically confirmed progressive bone-predominant mCRPC with two or more skeletal metastases on imaging , and no visceral disease .
Patients were treated with intravenous injections of radium-223, 55kBq/kg, every 4weeks for up to 6cycles . Concomitant treatment was permitted including abiraterone or enzalutamide, and bone supportive agents as previously described . Supportive care was delivered according to local institutional guidelines .
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