Also called: Hypoxic Radiosensitizers
Martin E. Liebling, M.D., FACP
Radiosensitizers are drugs that make cancer cells more sensitive to radiation therapy. Radiation therapy is one form of cancer treatment that prevents malignant cells from growing and dividing. Radiation treatments, however, can also damage normal cells. As a result, researchers are studying substances that can either make a tumor more sensitive to radiation without affecting healthy tissues, or that can shield normal cells from radiation.
Also known as hypoxic radiosensitizers, these drugs change the way cells respond to radiation. Radiosensitizers work to increase the normally low levels of oxygen found in cancer cells. Cancer cells that have normal or higher levels of oxygen are more receptive to radiation treatment. Radiosensitizers also make it more difficult for the cancer cells to repair themselves, and as a result, they die.
Another group of chemicals used to modify a cell’s response to radiation are radioprotectors. Also known as radioprotectants, these drugs protect normal cells while exposing cancer cells during radiation therapy.
As of 2007, the U.S. Food and Drug Administration (FDA) has not approved of any drugs for use as radiosensitizers. However, certain chemotherapy drugs already approved for cancer treatment are being studied for use as radiosensitizers. These include topotecan hydrochloride, paclitaxel and cisplatin. In addition, scientists are studying various drug compounds not yet approved or proven for the general patient population for use as radiosensitizers. Treatment with radiosensitizers is only available through clinical trials and patients must be approved by physicians to enroll in the study.
Radiosensitizers are drugs that make cancer cells more sensitive to radiation therapy. Radiation therapy is a method used to treat cancer. It uses x-rays, electron beams or radioactive isotopes to target and destroy cancer cells. Radiation is energy that a wave or a stream of particles can carry. This energy can alter the genetic code of a cell, preventing it from growing and dividing. Radiation is most effective in targeting cells that divide quickly, such as cancer cells. When cells are dividing, they are particularly vulnerable to damage.
Radiation therapy, however, can damage normal cells as well. When damage to normal cells occurs, it causes side effects (e.g., skin damage) that are usually temporary, but can be significant. As a result, researchers are searching for substances that can either make a tumor more sensitive to radiation without affecting healthy tissues, or that can shield normal cells from radiation.
One option being studied is the use of radiosensitizers. Also known as hypoxic radiosensitizers, these drugs change the way cells respond to radiation. They increase the effect of radiation on cancer cells by imitating oxygen, which the hypoxic (lacking oxygen) cancer cells need to survive. Cancer cells that have normal or high levels of oxygen are more receptive to radiation therapy.
A radiosensitizer is injected into a vein before radiation therapy. The patient is then instructed to breathe 100 percent oxygen before, during and after the radiation treatment. By increasing oxygenation at the time of treatment, radiosensitizers have the potential to increase the effectiveness of radiation therapy on cancer cells. Radiosensitizers also make it more difficult for the cancer cells to repair themselves, and as a result, they die.
Certain chemotherapy drugs are being tested for use as radiosensitizers in cancer treatment. These include:
|Generic Name(s)||Brand Name(s)|
|5-fluorouracil||5-FU, Adrucil, Efudex (topical), Fluorouracil|
|interferon alpha||IFN-±, Interferon-± 2a, Interferon-± 2b, Intron A, Roferon A|
In addition, a number of drugs not yet available to the general patient population are being studied for use as radiosensitizers in cancer treatment. Two promising radiosensitizers that are being investigated include RSR 13 (efaproxiral) and nimorazole. RSR 13 attaches itself to hemoglobin, a molecule in the blood that transports oxygen in the body. The drug changes the shape of the hemoglobin and allows oxygen to be released more easily to cancer cells. Clinical trials have suggested improved survival among glioblastoma patients who received both RSR 13 and radiation therapy. RSR 13 has also been studied in the treatment brain metastasis in breast cancer patients.
The second investigational drug, nimorazole, has been studied as a radiosensitizer in the treatment of head and neck cancers. Clinical trials have suggested that patients with laryngeal and pharyngeal cancers who received nimorazole along with radiation therapy demonstrated better control of the cancer with longer survival rates.
The U.S. Food and Drug Administration (FDA) has not yet given approval to any drugs as radiosensitizers. They are available in clinical trials and patients must be approved by physicians before being able to receive the drugs.
A radiosensitizer is injected into a vein before radiation therapy. The patient is then instructed to breathe 100 percent oxygen before, during and after the radiation treatment.
These drugs are being studied for use in the treatment of numerous types of cancer, including:
- Bile duct cancer and gallbladder cancer
- Breast cancer
- Head, neck and mouth cancers
- Liver and pancreatic cancer
- Prostate and testicular cancer
- Stomach cancer
- Brain tumors
- Ovarian cancer
Radioprotectors are another group of chemicals used to modify a cell’s response to radiation. Also known as radioprotectants, these drugs limit the injury of healthy cells that are damaged during radiation therapy.
Currently there is only one drug approved by the FDA for use as a radioprotector. Known as amifostine (Ethyol), the drug helps reduce the dry mouth that can occur when parotid glands (glands that help to produce saliva) receive a large dose of radiation. This may occur during treatment for salivary gland cancer or certain mouth and neck cancers. Researchers are studying the drug to determine if it can be used effectively as a radioprotector to treat other types of cancer as well. Additional studies are testing other chemicals for use as radioprotectors.
Conditions of concern with radiosensitizers
Before being enrolled in a trial for radiosensitizers, patients should inform their physician if they have been diagnosed with any of the following medical conditions:
- Chickenpox or recent exposure to chickenpox
- Heart disease, including congestive heart failure
- Kidney stones
- Liver disease
- Other forms of cancer
Use of radiosensitizers may be contraindicated for patients with certain conditions. A patient’s physician can best determine if the patient is a candidate for a clinical trial.
Potential side effects of radiosensitizers
Potential side effects of radiosensitizers vary from drug to drug. Common side effects include nausea, vomiting and diarrhea. Some patients may note numbness or tingling in the hands and feet. In addition, the drugs and treatment may cause a lower white blood cell count, increasing the risk of infection.
Less common side effects occurring with specific drugs include:
- Fetal abnormalities if pregnancy occurs while taking the drug
- Changes in taste, including a metallic taste to foods
- Increased sensitivity to the sun
- Mouth sores
- Hair loss or thinning
- Abdominal pain and constipation
Patients are encouraged to discuss the side effects of their specific drug with their medical oncologist or radiation oncologist.
Drug or other interactions
Patients should consult with their physicians before taking additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications. These drugs may interact with radiosensitizers.
Pregnancy issues with radiosensitizers
Before taking radiosensitizers, patients should inform their physician if they are attempting to become pregnant, are pregnant or are breastfeeding. Whether the patient is male or female, taking these drugs at the time of conception may cause birth defects. Birth defects may also occur when a woman takes the drugs during pregnancy. Patients taking these drugs are encouraged to use birth control. In addition, patients should inform their physician if they are planning to have children in the future because many drugs can cause infertility.
Questions for your doctor on radiosenstitizers
Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about radiosensitizers:
- Can these drugs be used for treatment of my cancer?
- Am I a candidate for a clinical trial with radiosensitizers?
- Which radiosensitizer would I receive?
- How will they be incorporated into my radiation therapy schedule?
- What are the risks associated with these drugs?
- How long will I need to take these drugs?
- What are the side effects associated with the type of drug I will be receiving?
- How effective are radiosensitizers for my type of cancer?
- Will they affect my fertility?
- Will the drugs interact with other cancer treatments?
- How will I know if the drugs are working?
- Am I taking any medications that could interfere with radiosensitizers?