Progress in the
Treatment of
Kidney Cancer
Presented byRonald M. Bukowski, MD
The Cleveland Clinic FoundationKeith Lyons, MSW
CancerCare
Find out about:
• Current treatment options • New advances
• The role of clinical trials • Ways to cope with cancer
National Office CancerCare 275 Seventh Avenue New York, NY 10001 Email: teled@cancercare.org Services Tel: 212-712-8080 1-800-813-HOPE (4673) Administration Tel: 212-712-8400 Fax: 212-712-8495 Email: info@cancercare.org Website: www.cancercare.org CancerCare is a national nonprofit organization that provides free professional support services to anyone affected by cancer: people with cancer, caregivers, children, loved ones, and the bereaved. CancerCare programs — including counseling, education, financial assistance, and practical help — are provided by trained oncology social workers and are completely free of charge. Founded in 1944, CancerCare now provides individual help to more than 90,000 people each year, in addition to the more than 1.4 million people who gain information and resources from our website.
Contacting CancerCare
If you are a health care professional interested in ordering bulk quantities of this booklet for your patients, please contact publications@cancercare.org.
Progress in the
Treatment of Kidney
Cancer
Presented by
Ronald M. Bukowski, MD
Director, Experimental Therapeutics Program The Cleveland Clinic Taussig Cancer Center Professor of Medicine
The Cleveland Clinic Foundation Lerner College of Medicine Case Western Reserve University Cleveland, Ohio
Keith Lyons, MSW
Oncology Social Worker CancerCare
New York, NY
The information in this booklet is based on the CancerCare Connect®
Telephone Education Workshop “Progress in the Treatment of Renal Cell Carcinoma,” which took place in January 2006. The workshop was conducted by CancerCare in partnership with the Association of Clinicians for the Underserved, Association of Oncology Social Work, Intercultural Cancer Council, Kidney Cancer Association, Multinational Association of Supportive Care in Cancer, and Society of Urologic Nurses and Associates.
This patient booklet was made possible by educational grants from Antigenics, Bayer/Onyx Pharmaceuticals, and Pfizer.
INTRODUCTION page 2
■ TREATMENT OPTIONS, page 4 ■ TARGETED TREATMENTS, page 6 ■ YOUR SUPPORT TEAM, page 10
FREQUENTLY ASKED QUESTIONS page 12
GLOSSARY (definitions of blue boldfaced words in the text) page 15
Researchers have made
exciting progress in
developing new
treatments.
Kidney cancer cells, highly magnified
E
ach year, 36,000 adults in the United States are diagnosed with kidney cancer. No one knows what causes this cancer, but it usually occurs for no obvious reason and is rarely inherited. Kidney cancer is two to three times more common in men than in women and tends to affect people between the ages of 50 and 70.Kidney cancer tends to be “silent,” causing no symptoms until it has spread beyond the kidneys. In fact, about 25 to 30 percent of kidney cancers have already spread to other parts of the body by the time they are diagnosed. The most common symptoms
are blood in the urine, pain or pressure in the side or back, and a lump in the side or back (see box on page 4).
There are several different types of kidney cancer cells. Knowing which type a tumor contains helps your doctor plan treatment. The most common, called clear cell, is found in about 80 percent of kidney tumors. The second
How the Kidneys Work
T
he two kidneys, which are each about the size of a fist, are located on both sides ofthe spine, in the back of the body.
The kidneys serve as the body’s filtration system. Each day they remove excess salts and other substances from the roughly 200 quarts of blood that flows through them.
In the process, the kidneys produce about two quarts of urine a day,
which carries waste out of the body. The kidneys also produce hormones that perform many functions, such as controlling blood pressure.
Each kidney works independently. People can live with only one kidney. If both kidneys fail to work, a dialysis machine can be used to filter the blood.
most common, called papillary, is found in about 10 to 12 percent of tumors. Other types, which occur rarely, include chromophobe, collecting duct, and undifferentiated cancer cells.
During the past ten years, researchers have made a number of important discoveries about how kidney tumors develop. For example, scientists have found changes in the genes that promote growth of kidney cancer. These types of findings have led to the development of new drugs recently approved for treatment of the disease.
Medical Illustration Copyright © 2006 Nucleus Medical Art. All rights reser
ved. www
Treatment Options
Surgery is the main treatment for kidney cancer that has not yet spread. One technique that surgeons are using more often is laparoscopy. For this technique, the surgeon inserts into the abdomen thin tubes that contain a tiny light, camera, and instruments to remove the tumor. This type of surgery is just as effective as traditional surgery, but less painful and easier to
People with kidney cancer may experience:
■ Blood in the urine
■ Pain or pressure in the side or back ■ A lump in the side or back
■ Ankle and leg swelling ■ High blood pressure
■ Anemia (low levels of red blood cells) ■ Weakness and fatigue
■ Loss of appetite ■ Weight loss ■ Frequent fevers
Signs and Symptoms
recover from.
If cancer has spread beyond the kidneys, it is usually treated with surgery (to remove as much of the tumor as possible) followed by immunotherapy. Immunotherapy is the use of substances that increase the body’s natural ability to fight cancer.
T
he stage of kidney cancer is based on the size of the tumor and whether it has spread to other parts of the body. Knowing the stage of the cancer helps determine the course of treatment. Kidney cancer is divided into four stages:Stage I The tumor is small (less than 7 centimeters) and has not spread beyond the kidney.
Stage II The tumor is larger than 7 centimeters. Stage III The tumor has either:
■ begun to grow out of the kidney, into the surrounding fat, or ■ spread to a nearby lymph node (lymph nodes are small,
bean-shaped structures that act as filtering stations to remove waste and fluids and help fight infection. When invaded by cancer cells, lymph nodes are a point from which tumors can spread throughout the body), or
■ spread to a large vein that drains the kidney.
Stage IV The tumor has spread into more than one lymph node, or it has spread extensively to other areas of the body, such as the lungs, bone, or brain.
Stages of
Kidney Cancer
Studies show that two such substances, interleukin-2
(Proleukin) and interferon alfa (Intron A, Roferon-A) can cause some kidney tumors to shrink by more than half. Doctors often prescribe these drugs as treatments for advanced kidney cancer, although, so far, only interleukin-2 has been approved by the US Food and Drug Administration (FDA) for this purpose.
Immunotherapy works in only 10 to 15 percent of patients, and it can cause severe side effects, such as extreme fatigue, heart attacks, and intestinal bleeding.
Targeted Treatments
Because standard treatments help only a relatively small percentage of people whose cancer has spread beyond the kidneys, researchers have been studying targeted treatments. Unlike chemotherapy, targeted treatments attack cancer cells primarily. This spares healthy tissues and causes fewer side effects. Today, the drug bevacizumab (Avastin), a targeted therapy approved for treatment of advanced colon or rectal cancer, is often prescribed for people with advanced kidney cancer. Also, two new targeted therapies, sorafenib (Nexavar) and sunitinib (Sutent), were approved by the FDA in late 2005 and early 2006, respectively, for the treatment of advanced kidney cancer.
BEVACIZUMAB
Although the FDA has approved bevacizumab only for treatment of advanced colon or rectal cancer, doctors
■ Smoking
■ Gender Kidney cancer is two to three times more
common in men than in women.
■ Race People of African descent are at highest risk for
kidney cancer.
■ Age Most people diagnosed with kidney cancer are
between the ages of 50 and 70.
■ Obesity and a high-fat diet ■ High blood pressure
■ Overuse of certain medications, such as diuretics (used
to increase urination) and milder types of pain medication
■ Exposure to the metal cadmium
■ Genetics Less than one percent of cases are inherited.
Tumors release VEGF, stimulating blood vessel growth, which, in turn, feeds tumor growth.
often prescribe it for people with advanced kidney cancer. Bevacizumab takes advantage of one of the things we know about how kidney tumors grow. Much like normal tissues, tumors need to have a blood supply.
Blood vessels grow in several ways. One way is through the presence of a protein called vascular endothelial growth
factor, or VEGF. This protein stimulates blood vessels to grow into tumors. When tumor cells spread through the body, they release VEGF to create new blood vessels. These blood vessels supply oxygen, minerals, and other nutrients to feed the tumor. Bevacizumab works by stopping VEGF from stimulating the growth of new blood vessels in tumors. Because normal tissues have an established blood supply, they are not affected by the drug.
Side effects of bevacizumab are generally mild. The drug may slightly increase the risk of a blood clot. It also sometimes raises blood pressure, which can be controlled with medications.
Researchers are still testing it alone and with other drugs for advanced kidney cancer. You may wish to talk with your doctor about whether bevacizumab is right for you.
SUNITINIB
In January 2006, the FDA approved sunitinib for treatment of advanced kidney cancer. Unlike bevacizumab and immunotherapy, which are given intravenously (through
VEGF
production Blood vesselgrowth Tumor growth
Tumor VEGF
The Importance of
Clinical Trials
T
here’s no question that clinical trials have led to advances in cancer treatment, creating a brighter future for all people with cancer. Clinical trials are the standard by which we measure the worth of new treatments and quality of life as patients go through those treatments. For this reason, doctors and scientists urge patients to take part.Your doctor can guide you in making a decision about whether a clinical trial is right for you. Here are a few things you should know:
■ Often, patients who take part in clinical trials gain access to
and benefit from new treatments.
■ Before you participate in a trial, you will be fully informed as
to the risks and benefits of the trial.
■ No patient receives a placebo or “dummy pill” if there is
a standard treatment available for the disease. Most trials are designed to test a new treatment against a standard treatment to find out whether the new treatment has any benefit.
■ You can stop taking part in a clinical trial at any time for any
reason.
a blood vein), sunitinib is a capsule that can be taken by mouth. It is taken daily for four weeks, followed by a two-week break before the next four-week cycle.
Research has shown that sunitinib can shrink kidney tumors in many people who have already tried other treatments that didn’t work. In one study, for example, sunitinib was given to people who had been treated with immunotherapy first. Within about two months of taking sunitinib, more than 40 percent of these people’s tumors had shrunk significantly. And, another 25 percent of patients’ tumors had shrunk, though not as much.
This response lasted for at least a year. The side effects of sunitinib, such as fatigue, are usually mild to moderate. Sunitinib works by targeting specific parts of cancer cells, cutting off their blood supply and blocking their ability to grow. Researchers believe that the drug’s dual action may enable it to control kidney cancer in the long run.
SORAFENIB
Another targeted treatment, called sorafenib, was approved to treat advanced kidney cancer in December 2005. Like sunitinib, it can be taken in pill form.
And, like sunitinib, sorafenib has been shown to shrink kidney tumors in many people who have already tried other treatments that didn’t work. In a study of more than 900 people, for instance, sorafenib shrank kidney tumors in about 80 percent of patients. In addition, it had a major effect on slowing tumor growth. Common side effects of the drug, such as loose stools, are generally mild and easy to treat.
Sorafenib helps stop cancer by suppressing VEGF and platelet
derived growth factor (PDGF). Like VEGF, PDGF is a protein that plays a critical role in the growth of blood vessels that feed kidney tumors. By inhibiting these vessels, sorafenib slows or stops their growth.
Sorafenib is also the first drug to target another protein, called
RAF kinase, which helps signal cancer cells to grow and multiply. Researchers suspect that these multiple actions are what make the drug so effective at slowing the advancement of cancer. Clinical trials of sorafenib are ongoing.
ON THE HORIZON
Researchers are continually looking for other ways to treat kidney cancer. Doctors in the United States and Europe are testing cancer vaccines, which help a person’s own immune system stall tumor growth. A number of vaccines are being
studied in clinical trials for people with advanced kidney cancer. Some types of vaccines are made from a person’s own tumor, whereas others are made from proteins on cancer cells or blood vessels in tumors.
Your Support Team
When you are diagnosed with kidney cancer, you’re faced with a series of choices that will have a major effect on your life, and maybe you’re not sure where to turn. But help is available. Of course, your most important resources are your health care team, family members, and friends. It is very important to develop good communications with them. You can also turn to these resources:
Oncology social workers and nurse practitioners
are specially trained to help you find out more about your treatment options, learn how to navigate the health care system, and get the best care possible. Kidney cancer can affect your energy level, the way you view yourself and the future, and other important areas of your life. Often when you are coping with kidney cancer, you need someone to talk with who
A vaccine is made using a patient’s own cells (1) that are injected. At the site of the injection (2), specialized immune cells recognize the vaccine and “present it” to the immune system (3). Once the vaccine is in the immune system it triggers an order to seek out and kill cancer cells, leaving healthy cells alone.
can help you and your family sort through the emotions and issues that arise. These health care professionals can provide emotional support, help you cope with treatment and its side effects, and guide you to resources. CancerCare® offers free
counseling from professional oncology social workers on its staff.
Support groups Support groups can reduce the feeling that you are going through cancer alone. These groups provide reassurance, suggestions, insight — a safe harbor where you can share similar concerns with your peers in a supportive environment. At CancerCare, people with cancer and their families can take part in support
The CancerCare Connect® booklet Coping With Cancer: Tools
to Help You Live provides more information on the medical,
emotional, and practical concerns faced by people with cancer. Request a copy of this booklet by calling CancerCare at 1-800-813-HOPE (4673).
groups in person, online, or on the telephone.
Financial help is offered by a number of organizations, including CancerCare, to assist with the cost of transportation to treatment, child care, or help needed around the home. CancerCare can also refer you to other resources in your community that can provide assistance.
Frequently Asked
Questions
Q
Is bevacizumab ever combined with sunitinib or sorafenib as a treatment for kidney cancer?A
Yes, this is taking place in clinical trials now. Combining the drugs has to be done very carefully, however, because some of the side effects of these medications are similar and their severity may be increased when they are taken together. For example, all of these drugs can raise blood pressure, so blood pressure would have to be checked frequently in someone who takes both drugs at the same time. Until the results of clinical trials are available, patients should not take more than one of these targeted treatments at a time.Q
Is sorafenib effective in tumors that contain papillary cancer cells? Or is it only helpful against tumors with clear cells?A
Sorafenib has been tested mainly in people with clear cell kidney tumors, the most common type. But some preliminary research suggests that the drug may also be effective in treating papillary tumors, the second most common type of kidney cancer. The FDA has approved the drug for treatment of all types of advanced kidney cancer. Until more is known about the effectiveness of sorafenib in treating papillary tumors, it makes sense to consider it as a treatment option for them.Q
I was taking sorafenib and my doctor decided to lower my dose because I was having trouble coping with the side effects of the drug. Is a lower dose of sorafenib as effective as the original, full dose?A
At this time, we don’t know. Lower doses may be just as effective as higher doses, but this has never really been tested in a clinical trial. That’s why we try to start all of our patients on the recommended dose and maintain that level. That doesn’t mean a reduced dose won’t work for you. We simply don’t know at this time.Q
Can people be treated with radiation while they are taking one of the new targeted treatments?A
Right now, we don’t have any research to show whether it would be safe to undergo radiation while taking one of these new drugs. Studies designed to test the safety and effectiveness of combining radiation with targeted treatment may be done in the future.Q
My husband has a small kidney tumor — about two to three centimeters. We know he needs surgery, but what happens after that?A
Generally, surgery is the only treatment required for tumors that small. Your doctor will discuss the type ofprocedure he or she recommends, but chances are the tumor will be removed with laparoscopy, a small opening in the abdomen. The surgeon will want to see your husband after the operation to make sure he is recovering well. After that, your medical oncologist will follow up with periodic blood tests to check kidney function, as well as chest x-rays and scans of the abdomen and chest to make sure the kidney tumor has not come back. You can expect your husband to have a checkup every three months for the first year, every four months for the second to fifth year, and yearly after that. Because there are currently no medicines that can prevent kidney cancer from coming back after surgery, it’s important to continue these screening tests. Like everyone, kidney cancer survivors should have regular screening tests for cancers of the prostate (in men) and colon. People
with kidney cancer may have a slightly higher chance of developing these types of cancers.
Q
I’m going to be treated with interleukin-2 for advanced kidney cancer. My doctor says I’ll have to be hospitalized during treatment. Why is that?A
Interleukin-2 is the most powerful drug currently used to treat advanced kidney cancer. High doses of interleukin-2 cause severe side effects in about 50 to 60 percent of people. These effects include low blood pressure, excess fluid in the lungs, kidney damage, heart attacks, bleeding, chills, and fever. As such, people treated with interleukin-2 need to be watched carefully in the hospital, for as long as 10 days. Only hospitals with expertise in treating people with high-dose interleukin-2 should recommend (or advise against) its use.Some doctors and hospitals use lower doses of interleukin-2, which have fewer and milder side effects. But lower doses do not seem to be as effective in treating kidney cancer as high doses of the drug.
Q
My doctor believes, and I agree, that sunitinib is right for me. But my health insurance doesn’t cover the cost. How can I get some financial assistance?A
Patient assistance programs are available to help cover the cost of many cancer drugs. If you are concerned about the cost of cancer treatment, contact CancerCare® to speak with a staffmember who can help you find these programs. CancerCare also provides limited financial assistance to individuals currently being treated for cancer to help with such costs as transportation and child care. Contact us at 1-800-813-HOPE (4673) to learn more.
Glossary
anemia A condition that can cause fatigue, shortness of breath, and other symptoms due to low levels of red blood cells.
dialysis A process in which a person’s blood is run through a machine that filters impurities. Dialysis is used in people whose kidneys are unable to filter blood.
immunotherapy The use of substances that increase the body’s natural ability to fight cancer.
laparoscopy Surgical removal of a kidney tumor through a small opening in the abdomen. The surgeon inserts thin tubes through the opening containing a tiny light, camera, and instruments to remove the tumor.
lymph nodes Small “filtering stations” that remove waste and fluids and help fight infections. When invaded by cancer cells, lymph nodes are a jumping-off point from which tumors can spread throughout the body.
PDGF Short for “platelet derived growth factor,” a protein that plays a critical role in promoting the growth of blood vessels that feed tumors.
RAF kinase A protein that helps signal cancer cells to grow
and divide.
response A drug’s effect on a tumor — either shrinking it or stopping its growth.
VEGF Short for “vascular endothelial growth factor,” a protein that stimulates blood vessels to grow in tumors. When tumor cells spread throughout the body, they release VEGF and create new blood vessels that supply the tumor cells with oxygen, minerals, and other nutrients.
Resources
CancerCare® 1-800-813-4673 www.cancercare.org
Kidney Cancer Association
1-800-850-9132
www.curekidneycancer.org
National Cancer Institute
Cancer Information Service 1-800-422-6237
www.cancer.gov
To find out about clinical trials:
Coalition of National Cancer Cooperative Groups www.CancerTrialsHelp.org
National Cancer Institute www.cancer.gov/clinicaltrials
dialogue and partnership about your cancer and your treatment.
All people depicted in the photographs in this booklet are models and are used for illustrative purposes only.
Photomicrograph of kidney cancer cells on page 2: Nancy Kedersha/ Immunogen/Photo Researchers, Inc.
rom the moment of diagnosis, let the hope begin.
F
Help and Hope
1-800-813-HOPE (4673) When Fran was diagnosed with
cancer, she knew that she and her daughter, Rachel, would need support. Both found help and hope with CancerCare. Since 1944, our professional oncology social workers have provided free counseling,
education and practical help for anyone touched by cancer. CancerCare is with you every step of the way.
If we can help you and your family, please call us at 1-800-813-HOPE (4673) or visit www.cancercare.org.
