Bisphosphonates In Metastatic Bone Disease
Two intravenous bisphosphonates have been Food and Drug Administration approved for the treatment of cancer. Pamidronate gained approval in 1995 for the prevention of disease-related skeletal events in patients with bone disease from multiple myeloma or bone metastases from breast cancer. Zoledronic acid gained approval in 2002 for the prevention of disease-related skeletal complications in patients with myeloma bone disease and bone metastases from prostate, breast or lung cancer. The FDA approved zoledronic acid in the wake of three large phase III trials that collectively enrolled over 3000 patients., , In men with metastatic castration-resistant prostate cancer , zoledronic acid reduces SREs. Zoledronic acid has not been shown to benefit men without bone metastases or men with hormone-sensitive bone metastases.
What Should I Do If I Have Pain
Let your doctor or nurse know about any pain you have as soon as possible. The earlier you ask for help, the easier it will be to get your pain under control. With the right treatment and management, your doctor and nurse should be able to help you control your pain.
Dont think that you are complaining too much or that you should put up with pain. You shouldnt have to accept pain as a normal part of having cancer. Pain will affect your daily life if it isnt properly controlled.
As well as treatments, there are things you can do yourself that might help with your pain.
What questions might my doctor or nurse ask about my pain?
Your doctor or nurse will ask you questions about your pain to try to get as much information about it as possible. This will help them work out the best treatment for you. They might ask you the following questions.
- Where is your pain?
- How bad is it?
- What does it feel like? For example, is it a stabbing pain, or a dull ache?
- When did the pain start? How often do you get it? How long does it last?
- Does it wake you at night?
- Does anything help?
- Have you tried any pain-relieving medicines? Did they help?
- Does anything make it worse?
- How does your pain make you feel? For example, do you feel anxious or depressed? Does this affect the pain?
- How does the pain affect your daily life?
Prostate Cancer Bone Metastasis
In the U.S., prostate cancer is the third leading cause of cancer death among men. It is estimated that about 1 out of 8 men will be diagnosed with PCa, and nearly one in 40 will die from it. If left untreated, prostate cancer tumors will grow, become more aggressive, and begin to metastasize to other areas of the body.
When a man is diagnosed with PCa, the doctor determines the extent of the cancer:
- Localized the cancer is confined to the prostate gland and capsule
- Regional the cancer has spread beyond the capsule to nearby tissues, e.g. seminal vesicles, prostate bed, pelvic lymph nodes
- Distant the cancer has spread to distant lymph nodes, bones or other organs, and systemic treatments are used to control but not cure the disease 1
PCa cells have certain molecular factors that give them a preference for spreading to bone. This is called prostate cancer bone metastasis, or bone mets. At this stage, treatment has two goals:
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Questions To Ask The Doctor
- What treatment do you think is best for me?
- Whats the goal of this treatment? Do you think it could cure the cancer?
- Will treatment include surgery? If so, who will do the surgery?
- What will the surgery be like?
- Will I need other types of treatment, too?
- Whats the goal of these treatments?
- What side effects could I have from these treatments?
- What can I do about side effects that I might have?
- Is there a clinical trial that might be right for me?
- What about special vitamins or diets that friends tell me about? How will I know if they are safe?
- How soon do I need to start treatment?
- What should I do to be ready for treatment?
- Is there anything I can do to help the treatment work better?
- Whats the next step?
Advanced Prostate Cancer And Bone Metastases
Most all prostate cancer patients worry about metastases. Metastases used to signal that death was near. Most prostate cancer metastases take place in bones. New treatments such as Xofigo have helped thousands of men delay health while maintaining a pain free high quality of life. Bone metastases are tumors that have spread from the prostate to your bones. Usually bone metastases occur in the pelvis, spine, thighs and ribs. But, they can develop in any bone anywhere in your body. Bone metastases can become extremely painful. Which is why it is reasonable and very human to fear bone metastases. So, if you are feeling anything that you imagine to be bone pain, talk to your doctor right away.
Diagnosing Bone Metastases
Bone metastases symptoms are sometimes confused with arthritis. The symptoms such as pain seem to be the same. So, if you are already diagnosed with prostate cancer, you must talk to your doctor about anything at all that you imagine to be pain in your bones. X-rays can diagnose bone metastases best, but bone scans, CT scans, PET scans, MRIs and blood tests are also used for diagnosis.
Untreated bone metastases in a man with castrate resistant prostate cancer could cause fractures and other skeletal problems none of which are pleasant.
Early detection of bone metastases allows more effective treatment to delay bone pain and other complications.
Preventing and Treating Bone Metastases
The most common side effects of Radium 223 are:
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What Questions Should I Ask My Healthcare Provider
If you have prostate cancer, you may want to ask your healthcare provider:
- Why did I get prostate cancer?
- What is my Gleason score? What is my Grade Group? What do these numbers mean for me?
- Has the cancer spread outside of the prostate gland?
- What is the best treatment for the stage of prostate cancer I have?
- If I choose active surveillance, what can I expect? What signs of cancer should I look out for?
- What are the treatment risks and side effects?
- Is my family at risk for developing prostate cancer? If so, should we get genetic tests?
- Am I at risk for other types of cancer?
- What type of follow-up care do I need after treatment?
- Should I look out for signs of complications?
A note from Cleveland Clinic
Prostate cancer is a common cancer that affects males. Most prostate cancers grow slowly and remain in the prostate gland. For a small number, the disease can be aggressive and spread quickly to other parts of the body. Men with slow-growing prostate cancers may choose active surveillance. With this approach, you can postpone, and sometimes completely forego, treatments. Your healthcare provider can discuss the best treatment option for you based on your Gleason score and Group Grade.
What Causes The Pain
We feel pain when our bones, muscles, organs, nerves or other parts of our bodies are damaged or irritated. Cancer which has spread into these areas might cause pain.
Sometimes pain can be due to cancer treatments. For example, radiotherapy to treat bone pain can sometimes cause your pain to get worse during treatment and for a few days afterwards. But this isnt very common.
Pain can also be caused by problems not linked to the cancer, such as an infection.
Your doctors and nurses will work with you to find out what is causing your pain and will talk to you about suitable treatments. There are effective ways to treat different types of pain.
Bone pain
If prostate cancer spreads to the bone, it can damage or weaken the bone and may cause pain. But not all men with cancer in their bones will get bone pain. Prostate cancer can spread to any area of bone around the body. It most commonly spreads to the spine. Pain in these areas can sometimes make it painful to walk and move around. The pain might remain in only one area, but over time it can spread to several parts of your body.
Bone pain is a very specific feeling. Some men describe it as feeling similar to a toothache but in the bones, or like a dull aching or stabbing. It can get worse when you move and can make the area tender to touch. Each mans experience of bone pain will be different. The pain may be constant or it might come and go. How bad it is can also vary and may depend on where the affected bone is.
Nerve pain
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Managing Bone Pain And Weakness
Symptoms like nausea, hot flashes, and pain can usually be relieved with medication. Some people find that complimentary treatments like acupuncture or massage help manage side effects.
Your doctor may also recommend orthopedic surgery to stabilize your bones, relieve pain, and help prevent bone fractures.
What Does Bone Cancer Feel Like
Cancer in bone can cause intermittent or progressively severe localized bone pain where the cancer is in the bone. The bone pain is described as aching, throbbing, stabbing, and excruciating. This can lead to insomnia, loss of appetite, and inability to carry out normal daily activities.
Sometimes cancer in bone weakens the bone to such a degree that it leads to breaking of the bone . This can cause severe bone pain and loss of function of the affected area of the body. Occasionally, bone fracture is the initial symptom of a bone cancer.
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Testing Options For Prostate Cancer
There is no one age for prostate cancer testing, but the American Cancer Society makes recommendations about screenings. According to the ACS, patients in any of these groups should consider asking their doctor about testing:
- Men age 50 or older who have an average risk of prostate cancer and a life expectancy of at least 10 more years
- Men age 45 or older with a high risk, including African-American men and those with a first-degree relative who had prostate cancer before age 65
- Men age 40 or older who have a higher risk, such as more than one first-degree relative diagnosed with prostate cancer at an early age
Rodent Models Of Pcibp
Rodent models of PCIBP involving intra-osseous injection of PCa cells with subsequent temporal development of hypersensitivity behaviours have been invaluable for generation of knowledge on the pathobiology of PCIBP and for the screening of novel molecules as potential analgesics/adjuvant agents for improved relief of this condition.
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Pharmacology Of Zoledronic Acid
Normal bone turnover involves a complex interaction between bone breakdown and bone turnover that is typically in equilibrium. Osteoclasts decompose bone matrix and mineral, allowing mononuclear cells to prepare bone surface for osteoblasts. In turn, osteoblasts lay down new matrix and bone substance. Estrogens and androgens help provide the milieu to maintain normal bone turnover. During the process of metastases, cancer cells create dysregulated bone turnover, with varying degrees of impaired osteolysis and bone synthesis seen depending on the type of cancer. For example, mixed osteoblastic and osteolytic metastases are commonly found in both prostate and breast cancer.
Zoledronic acid is a third generation nitrogen-containing bisphosphonate. Its core bisphosphonate moiety attaches to bone while its imidazole ring containing two nitrogen atoms confirms its potency. Zoledronic acid is approximately 100-fold more potent than pamidronate . Bisphosphonates have low intestinal absorption and can cause esophageal mucosal irritation if taken orally. For this reason, the formulated intravenous product is well absorbed and remains active in bone for some time.
Clinical Manifestations Of Bone Metastases
Pain is the most common symptom of bone metastases from prostate cancer. Fractures and spinal cord compression are also observed and can be debilitating. The vertebral bodies are the most common site of fracture, though pelvic, rib and long bone fractures are also seen. Disease-related fracture risk is particularly problematic given that androgen-deprivation therapy is the first-line treatment for metastatic prostate cancer. ADT itself erodes bone mineral density ,, , , , , accelerates bone turnover, and elevates fracture risk., , Low serum calcium due to its consumption and deposition by osteoblasts is common but is usually asymptomatic.
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Symptoms Point To Cancer’s Spread
Bone pain is often the first sign your cancer has extended into your bones. For instance, a man may experience lower from cancer that has spread into his pelvis.
Other warning signs occur if you have hypercalcemia, including and , , , and feeling very thirsty, sleepy, or confused.
Sometimes a in your arms, legs, or spine is the first sign that your cancer has spread. You may break a bone when you fall or just during your regular daily activities. If you do, you’ll feel sudden, severe pain. Get immediate treatmentespecially if the strikes in your back, a sign of a broken bone in your spine.
In other cases, bone metastasis has no symptoms at all.
What Are The Symptoms Of Advanced Prostate Cancer And Bone Metastases
When cancer cells spread to the bones, the condition weakens the very frame on which the body rests. The cells interfere with the strength and hardness of the bones structure, interrupting its normal cycle of building up and dissolving.
Theres no cure for advanced prostate cancer, but theres a lot that doctors can do to help with the symptoms that might develop. This includes managing pain. A common misconception is that if theres cancer in the bone, there must be pain, Tagawa says. Thats not true. Cancer can be in the bone without pain. However, if there is pain, he says, it can be controlled with anticancer therapies and pain medication, and good quality of life can be maintained.
In addition to pain, some men with bone metastases develop a condition called hypercalcemia, in which, because of the damage to bones from the cancer cells, too much calcium builds up in the blood. Hypercalcemia can make you feel constipated, thirsty, sleepy, or sluggish, and it can increase the urge to urinate, according to the ACS. Over time, hypercalcemia can cause muscle and joint achiness, as well as weakness in the muscles. In advanced stages, it can cause the kidneys to shut down.
There are treatments for hypercalcemia as well as for other complications from advanced prostate cancer, such as bones that become weak and break or fracture, and for growths in the spine that can press on the spinal cord and damage nerves.
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Bisphosphonates For The Prevention Of Bone Metastases
Bisphosphonates have not been shown to prevent bone metastases due to prostate cancer in the two randomized controlled trials that have evaluated them for this purpose.
The MRC Pr04 trial enrolled 508 men with locally advanced prostate cancer and a negative bone scan. They were randomized to a maximum of 5 years of either daily oral clodronate or placebo. With a median of almost 10 years of follow-up, no benefit was seen. There was a nonsignificant trend toward more new bone metastases with clodronate . After 281 deaths in follow-up, no improvement in OS was seen . Clodronate caused only mild increases in lactate dehydrogenase levels and in gastrointestinal complaints. The negative results of MRC Pr04 showed that the relatively weak bisphosphonate was not beneficial in men without metastatic disease.
The more potent zoledronic acid was evaluated in the Zometa 704 trial. Men with progression to CRPC were enrolled and randomized to zoledronic acid or placebo. The primary objective was to lengthen the time to development of the first bone metastasis. The study was placed on hold after only partial accrual due to a low event rate. It was later terminated. Comparison of the partial cohorts revealed no significant difference in the time to first metastasis.
Q What Is Bone Pain Like
Some men describe bone pain as feeling similar to a toothache but in the bones, or like a dull aching or stabbing. It can get worse with movement and make the bone tender to touch. Every mans experience of bone pain will be different. The pain may be continuous or it might come and go. How bad it is can also vary and it could depend on where the affected bone is.
If you have any pain in your back, hips or legs tell your doctor or nurse about it as soon as possible.
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Side Effects Of Chemotherapy
The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are used, and can include:
Mouth sores are also a side effect of chemotherapy. Your doctor may recommend treatments such as:
- Coating agents. These medications coat the entire lining of your mouth, forming a film to protect the sores and minimize pain.
- Topical painkillers. These are medications that can be applied directly to your mouth sores.
- Over-the-counter treatments. These include rinsing with baking soda or salt water, or magic mouthwash, a term given to a solution used to treat mouth sores. Magic mouthwash usually contains at least three of these ingredients: an antibiotic, an antihistamine or local anesthetic, an antifungal, a corticosteroid, and/or an antacid.
Chemotherapy can cause changes in the way food and liquids taste, including causing an unpleasant metallic taste in the mouth. Many people find that switching to plastic utensils helps. It may also help to avoid eating or drinking anything that comes in a can, and to use enamel-coated pots and pans for food preparation.
Early detection of bone metastases can help determine the best treatment strategy. It can also help ward off complications. Because men with prostate cancer bone metastases often experience painful episodes, pain management and improving quality of life are important goals of treatment.