Generic Name: radium 223 dichloride
Treatment for: Advanced Prostate Cancer
The U.S. Food and Drug Administration (FDA) has approved Xofigo (radium 223 dichloride) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastatic disease. Xofigo is the first alpha particle-emitting radioactive therapeutic agent approved by the FDA that has demonstrated improvement in overall survival (OS) and delay in time to first symptomatic skeletal event (SSE) compared to placebo, as shown in the pivotal Phase III ALSYMPCA trial.
Efficacy and Safety Data Supporting Xofigo Approval
The approval of Xofigo (radium 223 dichloride, radium 223) is based on data from the pivotal Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial. At the interim analysis, radium 223 significantly improved overall survival (OS) [HR=0.695 (95% CI 0.552-0.875), p=0.00185]; median OS was 14.0 months with radium 223 plus best standard of care vs. 11.2 months with placebo plus best standard of care. Additionally, at the interim analysis there was a delay in the time to first symptomatic skeletal event (SSE) for patients treated with radium 223 vs. placebo.
An updated analysis, conducted after the study was unblinded, showed a further improvement in overall survival (OS) for patients treated with radium 223 vs. placebo, with a median OS of 14.9 months vs. 11.3 months; HR=0.695 (95% CI 0.581-0.832).
The most common adverse reactions (greater than or equal to 10%) in patients receiving radium 223 in the ALSYMPCA trial were nausea, diarrhea, vomiting and peripheral edema. The most common hematologic laboratory abnormalities (greater than or equal to 10%) were anemia, lymphocytopenia, leukopenia, thrombocytopenia and neutropenia.
About Xofigo (radium 223 dichloride) Injection
Xofigo with the active ingredient radium 223 dichloride (radium 223) is an alpha particle-emitting radioactive therapeutic agent with an anti-tumor effect on bone metastases. Radium 223 mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The high linear energy transfer of alpha emitters may cause double-strand DNA breaks in adjacent cells, resulting in an anti-tumor effect on bone metastases. The alpha particle range from radium 223 is less than 100 micrometers, which may limit damage to the surrounding normal tissue.
About the ALSYMPCA Trial
The ALSYMPCA trial was a Phase III, randomized, double-blind, placebo-controlled international study of radium 223 dichloride with best standard of care vs. placebo with best standard of care in symptomatic CRPC patients with bone metastases. The trial enrolled 921 patients in more than 100 centers in 19 countries. The study treatment consisted of up to six intravenous injections of radium 223 or placebo each separated by an interval of four weeks.
The primary endpoint of the study was overall survival (OS). A key secondary endpoint was time to first symptomatic skeletal event (SSE), as defined as external beam radiation therapy (EBRT) to relieve skeletal symptoms, new symptomatic pathologic bone fracture, occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention.
Highlights of Prescribing Information
Indications and Usage
Xofigo is 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.
Dosage and Administration
The dose regimen of Xofigo is 50 kBq (1.35 microcurie) per kg body weight, given at 4 week intervals for 6 injections.
Dosage Forms and Strengths
Single-use vial at a concentration of 1,000 kBq/mL (27 microcurie/mL) at the reference date with a total radioactivity of 6,000 kBq/vial (162 microcurie/vial) at the reference date.
Contraindications
Pregnancy.
Warnings and Precautions
Bone Marrow Suppression: Measure blood counts prior to treatment initiation and before every dose of Xofigo. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after treatment. Monitor patients with compromised bone marrow reserve closely. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care measures.
Xofigo side effects
The most common adverse drug reactions (≥ 10%) in patients receiving Xofigo were nausea, diarrhea, vomiting, and peripheral edema.
The most common hematologic laboratory abnormalities (≥ 10%) were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.
To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Note: This document contains side effect information about radium 223 dichloride. Some of the dosage forms listed on this page may not apply to the brand name Xofigo.
Side effects requiring immediate medical attention
Along with its needed effects, radium 223 dichloride (the active ingredient contained in Xofigo) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor or nurse immediately if any of the following side effects occur while taking radium 223 dichloride:
More common
- Black, tarry stools
- bleeding gums
- bloating or swelling of the face, arms, hands, lower legs, or feet
- blood in the urine or stools
- chest pain
- chills
- cough
- fever
- lower back or side pain
- painful or difficult urination
- pale skin
- pinpoint red spots on the skin
- rapid weight gain
- sore throat
- sores, ulcers, or white spots on the lips or in the mouth
- swollen glands
- tingling of the hands or feet
- troubled breathing with exertion
- unusual bleeding or bruising
- unusual tiredness or weakness
Less common
- Confusion
- decreased frequency or amount of urine
- dizziness
- dry mouth
- fainting
- high fever
- hoarseness
- increase in heart rate
- increased blood pressure
- increased thirst
- lightheadedness
- loss of appetite
- nausea
- rapid breathing
- sunken eyes
- thirst
- vomiting
- weight gain
- wrinkled skin
Side effects not requiring immediate medical attention
Some side effects of radium 223 dichloride may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.
Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
- Diarrhea
Less common
- Redness, pain, and swelling at the injection site
For Healthcare Professionals
Applies to radium 223 dichloride: intravenous solution
General
The most common side effects (incidence of 10% or greater) were nausea, diarrhea, vomiting, and peripheral edema.
The most common hematologic laboratory abnormalities (incidence of 10% or greater) were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.[Ref]
Hematologic
Very common (10% or more): Anemia (93%), lymphocytopenia (72%), leukopenia (35%), thrombocytopenia (31%), neutropenia (18%)
Common (1% to 10%): Pancytopenia (2%)[Ref]
Gastrointestinal
Very common (10% or more): Nausea (36%), diarrhea (25%), vomiting (19%)[Ref]
Local
Common (1% to 10%): Erythema, pain, and edema at the injection site[Ref]
Other
Very common (10% or more): Peripheral edema (13%)
Common (1% to 10%): Dehydration (3%)
Renal
Common (1% to 10%): Renal failure and impairment (3%)
Patient Counseling Information
Advise patients:
- To be compliant with blood cell count monitoring appointments while receiving Xofigo. Explain the importance of routine blood cell counts. Instruct patients to report signs of bleeding or infections.
- To stay well hydrated and to monitor oral intake, fluid status, and urine output while being treated with Xofigo. Instruct patients to report signs of dehydration, hypovolemia, urinary retention, or renal failure / insufficiency.
- There are no restrictions regarding contact with other people after receiving Xofigo. Follow good hygiene practices while receiving Xofigo and for at least 1 week after the last injection in order to minimize radiation exposure from bodily fluids to household members and caregivers. Whenever possible, patients should use a toilet and the toilet should be flushed several times after each use. Clothing soiled with patient fecal matter or urine should be washed promptly and separately from other clothing. Caregivers should use universal precautions for patient care such as gloves and barrier gowns when handling bodily fluids to avoid contamination. When handling bodily fluids, wearing gloves and hand washing will protect caregivers.
- Who are sexually active to use condoms and their female partners of reproductive potential to use a highly effective method of birth control during treatment and for 6 months following completion of Xofigo treatment.