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Some types of cancer grow in response to sex hormones in the body. For example, most breast cancers have proteins called estrogen receptors and/or progesterone receptors on the surface of their cells. These cancers grow faster when exposed to the hormone estrogen. Likewise, most prostate cancers grow in response to male hormones called androgens, such as testosterone.
In cases where a cancer of unknown primary (CUP) is likely to be a breast or prostate cancer, hormone therapy may be an effective way to slow the growth of the cancer, or perhaps even shrink it, and may help you live longer.
For breast cancer, types of hormone therapy include drugs like tamoxifen, LHRH agonists like leuprolide (Lupron®) and goserelin (Zoladex®), and the aromatase inhibitors anastrozole (Arimidex®), letrozole (Femara®), and exemestane (Aromasin®). These drugs either lower estrogen levels or prevent cancer cells from being able to use it.
Hormone therapy can also be used to treat prostate cancer. Some commonly used drugs include LHRH agonists such as leuprolide and goserelin, and anti-androgens such as flutamide (Eulexin®) and bicalutamide (Casodex®). These drugs either lower the testosterone level or prevent cancer cells from being able to use it. Surgery to remove the testicles (orchiectomy) is another option.
Targeted therapy for cancer of unknown primary
Targeted therapy is a newer type of cancer treatment that uses drugs or other substances to identify and attack cancer cells while doing little damage to normal cells. These therapies attack the cancer cells’ inner workings – the programming that makes them different from normal, healthy cells. Each type of targeted therapy works differently, but all alter the way a cancer cell grows, divides, repairs itself, or interacts with other cells.
One target on squamous cell cancers of the head and neck is called epidermal growth factor receptor (EGFR). Cells from many of these cancers have too many copies of EGFR, which helps them grow faster and become more resistant to radiation or chemotherapy (chemo). A drug called cetuximab (Erbitux®) blocks EGFR, and can help patients with squamous cell cancers of the head and neck area. It’s often used along with radiation or chemotherapy (chemo), but it can also be used by itself to treat people whose cancers no longer respond to chemo and who can’t take radiation.
A number of targeted therapy drugs are used to treat breast cancer, including trastuzumab (Herceptin®), pertuzumab (Perjeta®), lapatinib (Tykerb®), and everolimus (Affinitor®).
Other targeted therapy drugs are used for cancers that start in other areas, and may be helpful in some cases of cancer of unknown primary.
Other drugs for cancer of unknown primary
Bisphosphonates
Bisphosphonates are drugs that are used to help strengthen and reduce the risk of fractures in bones that have been weakened by metastatic cancer. Examples include pamidronate (Aredia®) and zoledronic acid (Zometa®). They are given intravenously (IV). To treat cancer that has spread to bone, they are given once a month.
Bisphosphonates can have side effects, including flu-like symptoms and bone pain. They can also cause kidney problems, so people with kidney problems can’t use them. A rare but very distressing side effect of intravenous bisphosphonates is damage (osteonecrosis) in the jaw bones (ONJ). It can be triggered by having a tooth extraction (removal) while getting treated with the bisphosphonate. ONJ often appears as an open sore in the jaw that won’t heal. It can lead to loss of teeth or infections of the jaw bone. Doctors don’t know why this happens or how to treat it, other than to stop the bisphosphonates. Maintaining good oral hygiene by flossing, brushing, making sure that dentures fit properly, and having regular dental check-ups may help prevent this. Most doctors recommend that patients have a dental check-up and have any tooth or jaw problems treated before they start taking a bisphosphonate.
Denosumab
Like bisphosphonates, denosumab (Prolia®, Xgeva®) is a drug that can be used to strengthen bones and lower the risk of fractures in bones weakened by cancer spread. To treat cancer that has spread to bone, this drug is given as an injection under the skin, once a month.
Side effects include low levels of calcium and phosphate and ONJ. This drug does not cause kidney damage, so it is safe to give to people with kidney problems.
Octreotide
Octreotide (Sandostatin®) is an agent chemically related to a natural hormone, somatostatin. It’s very helpful for some patients with neuroendocrine tumors. If the tumor releases hormones into the bloodstream (which is rare in the poorly differentiated tumors that cause cancer of unknown primary), this drug can stop the hormone release. It can also cause tumors to stop growing or (rarely) to shrink. This drug is available as a short-acting version given as injection 2 to 4 times a day. It’s also available as a long-acting injection that needs to be given only once a month. A similar drug, lanreotide (Somatuline®), is also available. It’s also given as an injection once a month. These drugs are most likely to help treat cancers that show up on somatostatin receptor scintigraphy (OctreoScan).
If treatment for cancer of unknown primary stops working
If cancer keeps growing or comes back after one kind of treatment, it’s possible that another treatment plan might still cure the cancer, or at least shrink it enough to help you live longer and feel better. But when a person has tried many different treatments and the cancer has not gotten any better, the cancer tends to become resistant to all treatment. If this happens, it’s important to weigh the possible limited benefits of a new treatment against the possible downsides. Everyone has their own way of looking at this.
This is likely to be the hardest part of your battle with cancer – when you have been through many medical treatments and nothing’s working anymore. Your doctor may offer you new options, but at some point you may need to consider that treatment is not likely to improve your health or change your outcome or survival.
If you want to continue to get treatment for as long as you can, you need to think about the odds of treatment having any benefit and how this compares to the possible risks and side effects. In many cases, your doctor can estimate how likely it is the cancer will respond to treatment you are considering. For instance, the doctor may say that more chemo or radiation might have about a 1% chance of working. Some people are still tempted to try this. But it’s important to think about and understand your reasons for choosing this plan.
No matter what you decide to do, you need to feel as good as you can. Make sure you are asking for and getting treatment for any symptoms you might have, such as nausea or pain. This type of treatment is called palliative care.
Palliative care helps relieve symptoms, but is not expected to cure the disease. It can be given along with cancer treatment, or can even be cancer treatment. The difference is its purpose - the main purpose of palliative care is to improve the quality of your life, or help you feel as good as you can for as long as you can. Sometimes this means using drugs to help with symptoms like pain or nausea. Sometimes, though, the treatments used to control your symptoms are the same as those used to treat cancer. For instance, radiation might be used to help relieve bone pain caused by cancer that has spread to the bones. Or chemo might be used to help shrink a tumor and keep it from blocking the bowels. But this is not the same as treatment to try to cure the cancer.
At some point, you may benefit from hospice care. This is special care that treats the person rather than the disease; it focuses on quality rather than length of life. Most of the time, it’s given at home. Your cancer may be causing problems that need to be managed, and hospice focuses on your comfort. You should know that while getting hospice care often means the end of treatments such as chemo and radiation, it doesn’t mean you can’t have treatment for the problems caused by your cancer or other health conditions. In hospice the focus of your care is on living life as fully as possible and feeling as well as you can at this difficult time.
Staying hopeful is important, too. Your hope for a cure may not be as bright, but there’s still hope for good times with family and friends – times that are filled with happiness and meaning. Pausing at this time in your cancer treatment gives you a chance to refocus on the most important things in your life. Now is the time to do some things you’ve always wanted to do and to stop doing the things you no longer want to do. Though the cancer may be beyond your control, there are still choices you can make.
What’s new in research and treatment for cancer of unknown primary?
Research into the causes, diagnosis, and treatment of cancer is being done at many cancer research centers. Scientists are making progress in understanding how changes in a person’s DNA can cause normal cells to develop into cancer. A greater understanding of the gene changes that can occur in cancer is providing insight into why these cells become abnormal. Some of these advances may lead to better diagnosis and treatment of cancer of unknown primary (CUP).
Diagnosis
It’s very important that doctors are able to identify the origin of cancers of unknown primary so that the most effective treatments can be used. Immunohistochemistry and other lab tests can be very helpful in this regard, but they are not yet able to tell where all CUPs have started. Newer lab tests now becoming available will help classify CUP more precisely and predict a patient’s prognosis and response to treatment.
Hopefully at some point in the future, the number of cancers of unknown primary will drop dramatically, as doctors will be able to test tumor samples and determine what types of cancer they are.
Treatment
Because CUP represents a number of different types of cancer, it’s unlikely that a single treatment breakthrough will benefit all people with CUP. Still, progress in treating some of the more common types of cancer is likely to benefit people with CUP as well, especially if the cancers can be classified more accurately.
Some newer drugs called targeted therapies are being studied. These drugs have more selective effects than chemotherapy (chemo). Some of these, such as bevacizumab (Avastin®) and erlotinib (Tarceva®), are available to treat other cancers and have shown some activity in CUP. Clinical trials are being done to help determine who may benefit from targeted drugs and what drugs and combinations are best.
Cancer cells from CUP are sometimes tested in a lab to try to see which chemo drugs will be likely to work. Unfortunately, these tests don’t always do a good job of predicting the right chemo drugs. Many doctors don’t find them very helpful.
Many patients with cancer of unknown primary face a serious prognosis, so the need for advances in treatment is obvious. Clinical trials of new treatments are essential if progress is to occur. Some of these trials are testing new chemo drugs, new drug combinations, and new ways to give these drugs. Other clinical trials are studying new approaches to treatment, such as biological therapy, immunotherapy, and gene therapy. Because CUP is a very diverse category of many types of cancers, progress against CUP is likely to depend on continued progress toward understanding the molecular basis of all cancers.
