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Table of Contents Overview Questions and Answers About Newcastle Disease Virus Changes to This Summary (03/16/2006) General CAM Information Evaluation of CAM Approaches Questions to Ask Your Health Care Provider About CAM To Learn More About CAM
Overview
Questions and Answers About Newcastle Disease Virus
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What is Newcastle disease virus?
Newcastle disease virus (NDV) is a virus that causes a deadly infection in many kinds of birds. In humans, NDV causes mild flu-like symptoms or conjunctivitis (an infection of the eye that is also called pink eye) and/or laryngitis (an irritation and swelling of the voice box and the area around it).
Like other viruses, NDV infects cells (called host cells) and then uses those cells to replicate (make copies of) itself. Researchers are interested in NDV because it
replicates itself more quickly in human cancer cells than in most normal human cells and it can kill the host cells. For these reasons, the virus is being studied as a treatment for cancer.
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What is the history of the discovery and use of Newcastle disease virus as a complementary or alternative treatment for cancer?
The first report that NDV may be useful as a cancer treatment was published in 1964. For 20 years before this report, NDV was used in a vaccine to prevent Newcastle disease in birds. During that time, it was learned that NDV caused only minor illness in humans. The mild side effects caused by NDV in humans and its ability to replicate up to 10,000 times faster in human cancer cells than in most normal human cells, led researchers to look more closely at NDV as a possible cancer treatment.
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What is the theory behind the claim that Newcastle disease virus is useful in treating cancer?
There are many strains of NDV, and they may be either lytic or nonlytic for human cells. Lytic strains kill the infected cell by damaging its outer membrane (layer of tissue). Nonlytic strains kill by blocking the basic processes a cell needs to live. Lytic strains of NDV have been studied in humans because they can kill cancer cells directly, but both lytic and nonlytic strains have been used to make vaccines to help the immune system fight cancer.
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How is Newcastle disease virus administered?
The way NDV is given depends on how the virus is used to target cancer cells. It may be used to directly infect the patient with NDV or to make cancer vaccines. Cancer vaccines made with NDV may improve the body’s natural immune response to cancer, causing it to attack and kill more cancer cells than it would if the NDV were not present. Researchers are studying 3 ways of using NDV as a possible cancer treatment:
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Infection of the cancer patient with NDV
NDV can be injected directly into the tumor, a muscle, or a vein (intravenous injection), or into the colon. The virus can also be inhaled. As explained in Question 1 1, NDV infects cells and then replicates itself, creating more copies of the virus that can then infect cells throughout the body. This process targets and kills cancer cells by damaging the cells' outer membranes.
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Oncolysate vaccine.
Oncolysate vaccines are made using pieces of cancer cell membranes infected with NDV. Oncolysate-based vaccines are injected under or into the skin.
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Whole-cell vaccine
Whole-cell vaccines are made using whole tumor cells infected with NDV. The tumor cells used in the vaccine are changed in the laboratory so that they cannot multiply or infect the patient. Whole-cell vaccines with NDV are given only by injection under the skin.
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Have any preclinical (laboratory or animal) studies been conducted using Newcastle disease virus?
A number of preclinical studies have been done with NDV. Research in a laboratory or using animals is done to find out if a drug, procedure, or treatment is likely to be useful in humans. These preclinical studies are done before any testing in humans is begun. The following has been learned from preclinical studies:
- NDV replicates more quickly in human cancer cells than in any other type of cell.
- Some types of NDV are able to directly kill certain types of cancer cells.
- NDV and NDV-infected cancer cells can cause the immune system to respond in different ways.
A few of these studies used human cells, but most used animal cells. Based on these and other laboratory findings, clinical trials (research studies with people) using NDV were begun.
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Have any clinical trials (research studies with people) of NDV been conducted?
Clinical trials of NDV have been done but have not proven that NDV is effective as a cancer treatment. Some of the trials reported positive results and some did not. Most of the studies enrolled only small numbers of patients who also received standard treatments. None of the trials published in English were randomized and few were controlled. Randomized clinical trials give the highest level of evidence. In randomized trials, volunteers are assigned randomly (by chance) to one of 2 or more groups that compare different factors related to the treatment. In a controlled clinical trial, one group (called the control group) does not receive the new treatment being studied. The control group is then compared to the groups that receive the new treatment, to see if the new treatment works. Randomized controlled trials, enrolling larger numbers of people, are needed to confirm the results of studies done so far on the use of NDV to treat cancer.
Clinical trials studying the use of NDV as a cancer treatment have been done in the United States, Germany, and Hungary. Below are brief descriptions of these studies.
Studies Using Oncolysate Vaccines
Four clinical trials in the United States studied the use of NDV oncolysates in patients with metastatic melanoma. Three of these studies, a phase I clinical trial and 2 phase II clinical trials, were by the same group of researchers. Some positive results were found in these studies. The fourth trial was led by different researchers and showed no benefit. The same type of NDV was used to make the vaccines in all 4 studies, but the 2 groups of researchers used different methods to make them. Results from these studies need to be confirmed by randomized controlled trials that enroll larger numbers of people.
Two other phase II trials of NDV oncolysates were done in Germany. One of the studies showed that people in the trial had longer disease-free survival when compared with published information on similar patients who were treated with surgery alone. Because these studies were not controlled and the patients received other treatments, it is not clear if it was the treatment with NDV oncolysates that caused the responses reported.
Studies Using Whole-cell Vaccines
All published clinical studies of whole-cell vaccines with NDV have been done in Germany. Most of these studies involved patients with colorectal cancer, breast cancer, ovarian cancer, or renal cell (kidney) cancer. The same type of NDV was used to make the vaccines in all of the studies.
Some of these studies found improved disease-free survival or improved overall survival in patients treated with whole-cell vaccines. The lack of control groups and other weaknesses in study design and reporting made it unclear if benefits were caused by the whole-cell vaccine or by something else. Overall, the results showed that these vaccines may help the immune system kill more cancer cells during the vaccination program but may not provide long-term cancer immunity.
Studies Involving Infection with NDV (Including MTH-68)
Most research on the treatment of cancer by infecting patients with NDV has been done in Hungary, using the NDV strain MTH-68. The published findings include the following types of studies:
- An anecdotal report (incomplete descriptions of the medical and treatment history of one or more patients).
- A case report (a detailed report of the diagnosis, treatment, and follow-up of an individual patient).
- A small case series (a group of case reports involving patients who were given similar treatment).
- A phase II clinical trial.
According to the researchers, the MTH-68 treatment was helpful for most of the patients in these studies. The number of patients in the studies was small, however, and the patients in the clinical trial were not randomly assigned. The patients also received other treatments. For these reasons, it is not known if the patients were helped by the MTH-68 or by something else.
In the United States, a phase I clinical trial tested PV701, another type of NDV. In this trial, 79 patients with advanced cancers that were not helped by conventional therapy were given PV701 by injection into a vein. Some patients had partial responses to the treatment, while others did not have any change in their condition. More studies are planned.
One major concern is that repeated injections of NDV may cause a person's immune system to form antibodies against the virus. These antibodies would prevent NDV from infecting and killing cancer cells. More research is needed to study this.
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Have any side effects or risks been reported from NDV?
The side effects caused by NDV exposure have been mild to moderate. As noted in Question 1 1, NDV causes mild flu-like symptoms, conjunctivitis, and laryngitis in humans. Other side effects vary with how the virus is given.
- The most commonly reported side effect after treatment with the virus alone is fever, which usually goes away within 24 hours. In one study, inflammation and swelling were seen near some tumors. These complications may have contributed to the death of one patient.
- The most common side effects of treatment with NDV-infected whole-cell vaccines are minor:
- Mild headache.
- Mild fever on the day of the vaccination.
- Itching, swelling, and redness of the skin at the injection site.
- The only negative effect of treatment with the NDV oncolysate vaccine is inflammation at the injection site.
Studies that combined treatment with NDV oncolysates or whole-cell vaccines with substances called cytokines reported flu-like symptoms, fever, and swelling. The side effects seen in these studies have been linked to the cytokine portion of the treatment.
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Is Newcastle disease virus approved by the US Food and Drug Administration (FDA) for use as a cancer treatment in the United States?
The US Food and Drug Administration (FDA) has not approved Newcastle disease virus as a treatment for cancer.
Changes to This Summary (03/16/2006)
The PDQ cancer information summaries are reviewed regularly and updated as
new information becomes available. This section describes the latest
changes made to this summary as of the date above.
Editorial changes were made to this summary. General CAM Information
Complementary and alternative medicine (CAM)—also referred to as integrative medicine—includes a broad range of healing philosophies, approaches, and therapies. A therapy is generally called complementary when it is used in addition to conventional treatments; it is often called alternative when it is used instead of conventional treatment. (Conventional treatments are those that are widely accepted and practiced by the mainstream medical community.) Depending on how they are used, some therapies can be considered either complementary or alternative. Complementary and alternative therapies are used in an effort to prevent illness, reduce stress, prevent or reduce side effects and symptoms, or control or cure disease.
Unlike conventional treatments for cancer, complementary and alternative therapies are often not covered by insurance companies. Patients should check with their insurance provider to find out about coverage for complementary and alternative therapies.
Cancer patients considering complementary and alternative therapies should discuss this decision with their doctor, nurse, or pharmacist as they would any therapeutic approach, because some complementary and alternative therapies may interfere with their standard treatment or may be harmful when used with conventional treatment. Evaluation of CAM Approaches
It is important that the same rigorous scientific evaluation used to assess conventional approaches be used to evaluate CAM therapies. The National Cancer Institute (NCI) and the National Center for Complementary and Alternative Medicine (NCCAM) are sponsoring a number of clinical trials (research studies) at medical centers to evaluate CAM therapies for cancer.
Conventional approaches to cancer treatment have generally been studied for safety and effectiveness through a rigorous scientific process that includes clinical trials with large numbers of patients. Less is known about the safety and effectiveness of complementary and alternative methods. Few CAM therapies have undergone rigorous evaluation. A small number of CAM therapies originally considered to be purely alternative approaches are finding a place in cancer treatment—not as cures, but as complementary therapies that may help patients feel better and recover faster. One example is acupuncture. According to a panel of experts at a National Institutes of Health (NIH) Consensus Conference in November 1997, acupuncture has been found to be effective in the management of chemotherapy-associated nausea and vomiting and in controlling pain associated with surgery. In contrast, some approaches, such as the use of laetrile, have been studied and found ineffective or potentially harmful.
The NCI Best Case Series Program 5, which was started in 1991, is one way CAM approaches that are being used in practice are being investigated. The program is overseen by the NCI’s Office of Cancer Complementary and Alternative Medicine (OCCAM). Health care professionals who offer alternative cancer therapies submit their patients’ medical records and related materials to OCCAM. OCCAM conducts a critical review of the materials and develops follow-up research strategies for approaches deemed to warrant NCI-initiated research. Questions to Ask Your Health Care Provider About CAM
When considering complementary and alternative therapies, patients should ask their health care provider the following questions:
- What side effects can be expected?
- What are the risks associated with this therapy?
- Do the known benefits outweigh the risks?
- What benefits can be expected from this therapy?
- Will the therapy interfere with conventional treatment?
- Is this therapy part of a clinical trial?
- If so, who is sponsoring the trial?
- Will the therapy be covered by health insurance?
To Learn More About CAM
National Center for Complementary and Alternative Medicine (NCCAM)
The National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH) facilitates research and evaluation of complementary and alternative practices, and provides information about a variety of approaches to health professionals and the public.
- NCCAM Clearinghouse
- Post Office Box 7923 Gaithersburg, MD 20898–7923
- Telephone: 1–888–644–6226 (toll free) 301–519–3153 (for International callers)
- TTY (for deaf and hard of hearing callers): 1–866–464–3615
- Fax: 1–866–464–3616
- E-mail: info@nccam.nih.gov
- Web site: http://nccam.nih.gov
CAM on PubMed
NCCAM and the NIH National Library of Medicine (NLM) jointly developed CAM on PubMed, a free and easy-to-use search tool for finding CAM-related journal citations. As a subset of the NLM's PubMed bibliographic database, CAM on PubMed features more than 230,000 references and abstracts for CAM-related articles from scientific journals. This database also provides links to the Web sites of over 1,800 journals, allowing users to view full-text articles. (A subscription or other fee may be required to access full-text articles.) CAM on PubMed is available through the NCCAM Web site 6. It can also be accessed through NLM PubMed 7 bibliographic database by selecting the "Limits" tab and choosing "Complementary Medicine" as a subset.
Office of Cancer Complementary and Alternative Medicine
The NCI Office of Cancer Complementary and Alternative Medicine (OCCAM) coordinates the activities of the NCI in the area of complementary and alternative medicine (CAM). OCCAM supports CAM cancer research and provides information about cancer-related CAM to health providers and the general public via the NCI Web site 8.
National Cancer Institute (NCI) Cancer Information Service
U.S. residents may call the NCI Cancer Information Service toll free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 am to 4:30 pm. Deaf and hearing impaired callers with TTY equipment may call 1-800-332-8615. A trained Cancer Information Specialist is available to answer your questions.
Food and Drug Administration
The Food and Drug Administration (FDA) regulates drugs and medical devices to ensure that they are safe and effective.
- Food and Drug Administration
- 5600 Fishers Lane
- Rockville, MD 20857
- Telephone: 1–888–463–6332 (toll free)
- Web site: http://www.fda.gov/
Federal Trade Commission
The Federal Trade Commission (FTC) enforces consumer protection laws. Publications available from the FTC include:
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Who Cares: Sources of Information About Health Care Products and Services
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Fraudulent Health Claims: Don’t Be Fooled
- Consumer Response Center
- Federal Trade Commission
- CRC-240
- Washington, DC 20580
- Telephone: 1-877-FTC-HELP (1-877-382-4357) (toll free)
- TTY (for deaf and hearing impaired callers): 202-326-2502
- Web site: http://www.ftc.gov/
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Glossary Terms
anecdotal report
An incomplete description of the medical and treatment history of one or more patients. Anecdotal reports may be published in places other than peer-reviewed, scientific journals.
antibody (AN-tee-BAH-dee)
A type of protein made by plasma cells (a type of white blood cell) in response to an antigen (foreign substance). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.
breast cancer (brest KAN-ser)
Cancer that forms in tissues of the breast, usually the ducts (tubes that carry milk to the nipple) and lobules (glands that make milk). It occurs in both men and women, although male breast cancer is rare.
cancer (KAN-ser)
A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.
cancer vaccine
A vaccine designed to prevent or treat cancer.
case report
A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin).
case series
A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment.
cell (sel)
The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
clinical trial
A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical study.
colon (KOH-lun)
The longest part of the large intestine, which is a tube-like organ
connected to the small intestine at one end and the anus at the other. The
colon removes water and some nutrients and electrolytes from partially
digested food. The remaining material, solid waste called stool, moves
through the colon to the rectum and leaves the body through the anus.
colorectal cancer (KOH-loh-REK-tul KAN-ser)
Cancer that develops in the colon (the longest part of the large intestine) and/or the rectum (the last several inches of the large intestine before the anus).
conjunctivitis
A condition in which the conjunctiva (membranes lining the eyelids and covering the white part of the eye) become inflamed or infected. Also called pinkeye.
control group
In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.
controlled clinical trial
A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all.
conventional therapy (kun-VEN-shuh-nul THAYR-uh-pee)
A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment.
cytokine (SY-toh-kine)
A substance that is made by cells of the immune system. Some cytokines can boost the immune response and others can suppress it. Cytokines can also be made in the laboratory by recombinant DNA technology and used in the treatment of various diseases, including cancer.
disease-free survival (dih-ZEEZ... ser-VY-vul)
The length of time after treatment for a specific disease during which a patient survives with no sign of the disease. Disease-free survival may be used in a clinical study or trial to help measure how well a new treatment works.
drug
Any substance, other than food, that is used to prevent, diagnose,
treat or relieve symptoms of a disease or abnormal condition. Also refers
to a substance that alters mood or body function, or that can be
habit-forming or addictive, especially a narcotic.
Food and Drug Administration
FDA. An agency in the U.S. federal government whose mission is to protect public health by making sure that food, cosmetics, and nutritional supplements are safe to use and truthfully labeled. The Food and Drug Administration also makes sure that drugs, medical devices, and equipment are safe and effective, and that blood for transfusions and transplant tissue are safe. Also called FDA.
host cell
A cell that is infected by a virus or another type of microorganism.
immune response (ih-MYOON reh-SPONTS)
The activity of the immune system against foreign substances (antigens).
immune system (ih-MYOON SIS-tem)
The complex group of organs and cells that defends the body against infections and other diseases.
infection
Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.
inflammation (IN-fluh-MAY-shun)
Redness, swelling, pain, and/or a feeling of heat in an area of the body. This is a protective reaction to injury, disease, or irritation of the tissues.
inhalation
In medicine, refers to the act of taking a substance into the body by breathing.
injection
Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."
intravenous injection (IN-truh-VEE-nus in-JEK-shun)
Injection into a vein.
laryngitis
Inflammation of the larynx.
lytic
Having to do with lysis. In biology, lysis refers to the disintegration of a cell by disruption of its plasma membrane. Lysis can be caused by chemical or physical means (e.g., high-energy sound waves) or by a virus infection.
melanoma (MEH-luh-NOH-muh)
A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.
membrane
A very thin layer of tissue that covers a surface.
metastatic (meh-tuh-STA-tik)
Having to do with metastasis, which is the spread of cancer from one part of the body to another.
Newcastle disease virus (NOO-ka-sul dih-ZEEZ VY-rus)
NDV. A bird virus that is being studied in the treatment of cancer. It may be used to kill cancer cells directly, or it may be given as a cancer vaccine to stimulate the body’s immune system. Newcastle disease virus is a type of biological response modifier and vaccine therapy. Also called NDV.
nonlytic
In biology, refers to viruses that do not kill infected cells by disrupting their plasma membranes.
oncolysate
An extract made from cancer cells that are infected with a lytic strain of virus. The extract contains both cancer cell proteins and virus proteins. Oncolysates are being studied as cancer vaccines.
ovarian cancer (oh-VAYR-ee-un KAN-ser)
Cancer that forms in tissues of the ovary (one of a pair of female reproductive glands in which the ova, or eggs, are formed). Most ovarian cancers are either ovarian epithelial carcinomas (cancer that begins in the cells on the surface of the ovary) or malignant germ cell tumors (cancer that begins in egg cells).
overall survival rate (... ser-VY-vul ...)
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. The overall survival rate is often stated as a five-year survival rate, which is the percentage of people in a study or treatment group who are alive five years after diagnosis or treatment. Also called survival rate.
partial response (PAR-shul reh-SPONTS)
A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.
PDQ
PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.
phase I trial
The first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection) and the best dose. The dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments.
phase II trial
A study to test whether a new treatment has an anticancer effect (for example, whether it shrinks a tumor or improves blood test results) and whether it works against a certain type of cancer.
preclinical study
Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done.
PV701
A virus that is being studied in the treatment of cancer. It belongs to the family of viruses that cause Newcastle disease in birds.
randomized clinical trial
A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial.
renal cell cancer
The most common type of kidney cancer. It begins in the lining of the renal tubules in the kidney. The renal tubules filter the blood and produce urine. Also called hypernephroma.
replicate
To make a copy or duplicate of something.
side effect
A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.
surgery (SER-juh-ree)
A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.
symptom
An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.
tumor (TOO-mer)
An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancerous), or malignant (cancerous). Also called neoplasm.
vaccination
Treatment with a vaccine.
vaccine
A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. A vaccine can help the body recognize and destroy cancer cells or microorganisms.
virus (VY-rus)
In medicine, a very simple microorganism that infects cells and may cause disease. Because viruses can multiply only inside infected cells, they are not considered to be alive.
whole cell vaccine
Vaccine made from whole tumor cells that have been changed in the laboratory.
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Table of Links
1 | http://cancer.gov/cancertopics/pdq/cam/NDV/patient/33.cdr#Section_33 |
2 | http://cancer.gov/cancertopics/pdq/cam/NDV/patient/35.cdr#Section_35 |
3 | http://cancer.gov/cancertopics/pdq/cam/NDV/patient/37.cdr#Section_37 |
4 | http://cancer.gov/cancertopics/pdq/cam/NDV/patient/39.cdr#Section_39 |
5 | http://www.cancer.gov/cam/bestcase_intro.html |
6 | http://www.nlm.nih.gov/nccam/camonpubmed.html |
7 | http://www.ncbi.nlm.nih.gov/PubMed |
8 | http://www.cancer.gov/cam |
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