What About Xofigo?
  1. Xofigo is 223Ra dichloride, is a pure α emitter, and is consider a treatment for metastatic bone cancer that's primary comes from the prostate
    1. Should it be used?
      1. Patients that have castration resistant prostate cancer(CRCP)
      2. No visceral metastatic mass
      3. Has symptoms of metastatic bone disease causes by CRPC
    2. Survival rates
      1. One study showed that when compared to a placebo the mean survival went from 11.3 months to 14.9 months
      2. A second study has a mean survival rate of 14.0 months with Xofigo and 11.2 with placebo
      3. In addition, it can relieve bone pain due to painful bony mets
    3. Safety issues
      1. The website sates that it is contraindicated in woman that are pregnant. Hm??
      2. Myelosuppression
        1. The following has been reported to occur with Xofigo: thrombocytopenia, neutropenia, pancytopenia, and leukopenia
        2. There are small percentages of bone marrow failure, but most of those patient already had failing or failed bone marrow prior to the Xofigo injection
        3. It is apparent that there is some myelosuppression associated with this radiotracer
      3. Hematological assessment
        1. Base line prior to dosing should be as follows: ≥1.5 x 109/L neutrophils count, ≥100 x 109/L platelet count and hemoglobin ≥10g/dL
        2. Normal range for platelets is 150 to 400 x 109/L or 150k to 450k μL
        3. Post administration the value can drop to: ≥1.0 x 109 neutrophils, ≥50 x 109 platelets. Should these levels drop below this and do not recover within 6 to 8 weeks another dose of Xofigo is not recommended
      4. No additional chemo or radiation therapy should be administered. While this has not been assessed, chemo/radiation therapy could further complicate myelosuppression
      5. Radiation exposures is a concern
        1. This is an α emitter and while it travels very short distances in air it could cause problems if exposures to the surface of your skin or the lining in your GI track
        2. Avoid all body fluids if possible, however, use gloves if cleanup becomes necessary
        3. Loss of body fluids, such as vomiting can occur after administration, therefor be aware of patient dehydration
      6. Establish an IV site with a saline drip. Do not subcutaneously inject the dose. 1% of patients had erythema, pain, and edema at the site of injection
      7. Pathophysiology
        1. 223Ra is an analog of Ca
        2. Forms a complex with the hydroxyapatite in areas of high bone turnover
        3. α-emitter has a LET of 80keV/μm and travels less than 100μm (< 10 cell diameter)
        4. Causes double strain DNA breaks to tumor cells
        5. Fifteen-minutes post dose 20% remains in the vascular pool, 4% in 4 hours, <1% in 24 hours
        6. Four hours post dose 61% of the dose is found in the bone and 49% in the intestine
        7. Sixty-three percent is excreted within 7 days and at 48 hours 13% was fecal where only 2% was found in urine
      8. Possible secondary malignancies
        1. While this is a concern, the placebo had a greater occurrence when compared to Xofigo (2% vs <1%)
        2. Latent period for truly assessing this could not be done because it patients were not followed after the clinical trials were over
        3. I have to wonder, how many patients lived long enough to truly test these secondary effect?
        4. Or how much radiation the patients received prior to the Xofigo?
      9. Reports of adverse reaction
        10. Adverse Event Xofigo Placebo
        Nausea 36% 35%
        Diarrhea 25% 15%
        Vomiting 19% 14%
        Peripheral Edema 13% 10%
        Grade 3 and 4 Adverse Events 57% 63%
        Anemia 93% 88%
        Lymphocytopenia 72% 53%
        Leukopenia 35% 10%
        Thrombocytopenia 31% 22%
        Neutropenia 18% 5%

    4. The dose is calculated by the above formula and administered in a volume
      1. Dose is always calibrated at 24μCi/mL
      2. Must determine the actual amount amount of activity per mL by applying the decay factor
    5. Questions that I cannot answer
      1. When is the patient's body fluids no longer contain radioactive?
      2. When administering the dose, how slowly should dose be given?
      3. If we are measuring an alpha emitter can our dose calibrator measure it?
      4. Other questions?

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    10/23

    Suggested reading - Radium-223 for Metastatic Castrate-Resistant Prostate Cancer by Kunal K. Sindhu, MD, et.al.

    References:
    1 - Xofigo website - http://www.xofigo-us.com/index.php?ecid=xofigo:ps:de:tl:othd:41418:221
    2 - Package insert - http://labeling.bayerhealthcare.com/html/products/pi/Xofigo_PI.pdf