the day. There are two types of cells that bone relies on to build healthy new bone. The osteoblasts help to build new bone and act to simply “fill in potholes on the road,” so to speak. In contrast, the osteoclasts create the potholes, for good and bad reasons. In healthy bones, osteoclasts function to break down bone so that osteoblasts can put healthy bone back in areas of the bone that need repair. Xgeva and Zometa simply work by blocking or inhibiting the ability of osteoclasts to function. In this way, the skeleton stops losing any more bone and may even build a little new bone.
Prostate cancer can increase the action of the osteoclasts, causing more bone breakdown, but it especially increases the tendency of the osteoblasts to build abnormally weak bone. This is why prostate cancer has been known for years as a cancer that causes osteoblastic bone disease. By reducing the ability of the osteoclasts to do an abnormal amount of damage, Xgeva and Zometa are effective at reducing bone loss and SREs in prostate cancer patients.
Question: Why does prostate cancer tend to travel to the bones more as compared to most other body sites?
Answer: Bone releases or produces a large number of compounds to which prostate cancer is attracted, more so than most other locations in the body. There is research ongoing to attempt to discover everything related to bones that prostate cancer finds attractive to determine whether production of these compounds can be shut off in order to fight the cancer. It is plausible that Xgeva and Zometa and other osteoporosis drugs may work partly by shutting off the production of some of these compounds.
Question: When prostate cancer goes into the bone, is this the same thing as “bone cancer” or “cancer of the bones”?
Answer: No. Cancer that starts in the bone is very different. Cancer that starts in the prostate and eventually goes into the bone can be associated with minimal to major problems. There can be a single tumor at one bone site or many tumors located in many bone sites from head to toe. The impacts of cancer that goes to the bones vary in each person.
Question: When during the course of HRPC is it best to start Xgeva or another bone-protecting drug?
Answer: Research has demonstrated that the earlier these drugs are taken in the course of HRPC, the better the results. In fact, it is best to start the drugs before there is any cancer-related bone pain, but they still work well at most time periods. It is not usual for men to have received them or another bone-health drug before being diagnosed with HRPC. Some men are given Xgeva or Zometa the moment they start on hormone therapy for any stage of cancer. You will discuss treatment intervals with your physician. More treatments can equate to more benefit, but also can increase the risk of rarer side effects. For this reason, some experts suggest limited treatment with Xgeva or Zometa as opposed to continuous use. There are clinical trials considering treatment frequency, so be aware that the timing and length of treatment need to be a matter of ongoing discussion.
Question: Do these drugs help with other types of cancer?
Answer: Yes. These drugs have also been shown to be a benefit in breast, kidney, and lung cancers and multiple myeloma (cancer of the immune cells of the bone marrow). These are also exactly the same drugs used currently by some post-menopausal women to prevent bone loss from osteoporosis. As you can see, these drugs have fairly diverse applications in the area of bone health.
Radiopharmaceutical Drugs
| SAMARIUM-153 | STRONTIUM-89 |
| Also known as Quadramet | Also known as Metastron |
| How is it taken? IV | How is it taken? IV |
| Approval status FDA approved | Approval status FDA approved |
| Company EUSA-Pharma Inc. | Company Amersham Healthcare and AstraZeneca |
Advantages Radiopharmaceutical drugs (radioactive IV drugs) are given several times over a period of weeks to months, in general. They are used to treat pain when cancer has gone into the bones. Once the drug is given, it goes through the body seeking cancerous areas and emits energy particles that kill some of the cells. Many individuals get some pain relief in the first week. Only one of these drugs can be given. They are never given in combination. In conjunction with chemotherapy, each may provide a survival benefit.
The catch The side effects from these drugs result from radiation that goes into the bone and can cause blood cell production (of white blood cells and platelets) to be reduced. Less commonly, diarrhea can occur. The half-life of the drug samarium is much shorter than that of strontium; it seems to cause fewer bone marrow side effects because it emits radiation for a shorter time. Therefore, samarium has become more popular lately among some men with HRPC.
What else do I need to know? A newer radiopharmaceutical, Alpharadin (radium-223), involves alpha radiation, which generally travels a shorter distance compared to beta radiation drugs (such as samarium and strontium), so the benefit-to-risk ratio may be better for patients (see chapter nine). Regardless, all of these medications work well and are probably underused in HRPC patients with bone pain.
Other Non-Bisphosphonate Bone Health Drugs
As a final thought in this area, we should mention other bone-health drugs that are not in the bisphosphonate drug class. There are several available, including:
• Calcitriol (pills) should not be used by most patients. It was combined with chemotherapy in a recent trial of men with HRPC. It did not improve their condition and may have even made it a little worse.
• Estrogen (see also the secondary hormonal treatments chapter), a partially effective secondary hormonal therapy, has cardiovascular side-effect issues, so it is not a popular osteoporosis drug for HRPC.
• Parathyroid hormone (PTH or Forteo, an injection) is an effective FDA-approved osteoporosis drug for men and women, but it is not being used in cancer patients because of a lack of research in this area.
• Strontium ranelate (pills, not FDA approved) is an effective drug used around the world, but it has not been tested enough in cancer patients. The same is true for strontium dietary supplements.
• Raloxifene (Evista, a pill) is FDA approved for osteoporosis, but not in HRPC because of a lack of research and also because it increases the risk of blood clots.
• Toremifene (pill) is not FDA approved for prostate cancer and may increase the risk of blood clots.
The bottom line is that when it comes to HRPC, the only FDA-approved drugs to reduce SREs are Xgeva or Zometa.
Notes
PROVENGE
Also known as sipuleucel-T
How is it taken? infusion
Approval
