Reducing and Preventing Radiation Side Effects

 

There are several ways to prevent radiation therapy side effects. These include altering how the radiation is delivered and administering drugs to protect normal cells from radiation damage.

One new delivery method lessens the intervals between radiation treatments to give cancer cells less time to recover. Others provide more specific targeting and dose control. Drug therapy advances help shield healthy tissue from radiation and treat the changes it may cause.

Radiation Delivery Methods

Two delivery methods that were originally used to reduce radiation side effects are dose fractionation, or splitting the total dose of radiation therapy into multiple doses, and physical shielding with lead blocks to reduce the area of exposure.

Fractionation and hyperfractionation - Radiation therapy was originally given in one large dose. More than half a century ago it was found that it was less toxic and more effective to administer radiation on a daily basis, a method called dose fractionation. Fractionation allows the delivery of a larger total dose of radiation to the cancer than would have been possible as a single dose.

Currently, most radiation treatments are administered daily, 5 days a week—strictly for the convenience of maintaining a normal work week. The 24-hour interval and the 2-day interval between doses allows for recovery of normal tissue between doses; cancer cells, in general, have less recovery ability. There is no doubt that using fractionation has reduced side effects compared with single-dose delivery.

Although cancer cells tend to be less resilient than normal tissue, there is a chance that the intervals between fractionated doses of radiation may allow cancer cells to recover. Recent findings indicate that some cancers are best treated by reducing the 24-hour interval between doses to 6 to 8 hours to enhance the toxic effects on cancer cells while still preserving an adequate time interval for the recovery of normal cells. This technique, called hyperfractionation, is being widely used to treat a variety of cancers. Hyperfractionation requires sophisticated equipment, so it is important for patients to be treated at specialty medical centers that have experience and staff trained in this technique.

Intensity-modulated radiation therapy (IMRT) - IMRT delivers varying intensities of radiation with a rotating device. The intensity is varied by the placement of “leaves,” which either block or allow the passage of radiation. The rotating component of this technique allows for more specific targeting of the cancer, sparing normal tissue from damage caused by radiation exposure.

In conventional radiation therapy, the beam is usually delivered from several different directions, up to 5 or 10. The greater the number of beam directions, the more the dose will be confined to the target cancer cells, sparing normal cells from exposure. IMRT delivers radiation from every point on a helix, or spiral, rather than only a few points.

IMRT is similar to CT scanning. In CT, a beam rotates around the patient, creating a sequence of cross-sectional images. IMRT also uses a rotating beam, but the beam delivers radiation. IMRT also delivers treatment one cross section at a time.

Three-dimensional conformal radiation therapy (3-D CRT) - Three-dimensional conformal radiation therapy is a promising approach for the treatment of some cancers. Using computerized tomography (CT) and other scans, radiation oncologists have developed methods of determining the tumor size and shape in three dimensions.

This allows high-dose external beam radiation therapy to be delivered primarily to the cancer with less damage to normal cells. For example, three-dimensional conformal radiation has allowed radiation oncologists to reduce the amount of radiation to the breast by 50 percent, which should decrease the risk of secondary breast cancer. It is important for conformal radiation to be administered at special cancer centers with sophisticated equipment and trained staff.

Drug Therapy

Although preventing radiation side effects is the ideal, sometimes side effects are inevitable. In these situations, several types of drugs can be used to decrease them. Drug therapies for radiation-induced side effects fall into two categories:

  1. Those that protect the noncancerous tissue from radiation damage through systemic administration
  2. Those that are applied topically to mucus membranes to decrease or treat radiation damage

Radiation protectors - Radioprotectants are drugs that selectively protect normal cells, but not cancer cells, from the effects of radiation. Over the past 50 years, many radiation protectors have been tested in laboratories to determine how well they prevent radiation damage to normal cells and tissues.

Ethyol® (amifostine)- Amifostine is a radiation protector and the only drug that has been approved by the FDA for xerostomia (dry mouth) in patients receiving radiation therapy for cancers of the head and neck. Xerostomia is a chronic dry-mouth condition caused by damage from radiation therapy to the salivary glands. Xerostomia can greatly impair a patient’s ability to speak, chew, swallow, and taste and can have a negative effect on quality of life.

Results from a clinical trial indicated that the incidence of severe xerostomia in patients receiving amifostine was 51 percent, compared with 78 percent for patients receiving radiation therapy alone. One year after completion of radiation therapy, only 35 percent of patients who had received amifostine were still experiencing symptoms of xerostomia, whereas 57 percent of patients who had received radiation therapy alone were still experiencing symptoms.

Steroids - Steroids are naturally occurring hormones produced by the adrenal glands. As part of your radiation therapy treatment, your physician may prescribe a steroid, such as Prednisone® or Decadron® (dexamethasone). These drugs help decrease swelling in body tissues. Dexamethasone has also been shown to prevent radiation-induced vomiting, especially in treatment of cancers of the abdomen.

Topical agents - Some drugs can be applied topically to mucous membranes to decrease or treat radiation damage. The topical agent sucralfate may protect mucous membranes and is often used during and after radiation therapy to prevent and treat mucositis (mouth sores).

Topical antiseptics, such as chlorhexidine and benzydamine, have been used for the prevention of mucositis, but recent research indicates that these are not effective. In a Mayo Clinic study involving 52 patients with head and neck cancers who received radiation therapy, chlorhexidine was found to be more toxic and no more effective than a placebo in the prevention of mucositis.

German researchers reported that chlorhexidine mouthwashes were not effective in treating mucositis in patients with a low white blood cell count. Despite a significant decrease in aerobic and anaerobic bacteria on the oral mucous membranes, the risk of mucositis seemed to be enhanced. The patients treated with chlorhexidine seemed to have more problems with inflammation, resulting in mucositis.

Strategies to Improve Prevention and Management of Radiation Side Effects

To develop more effective cancer treatments, new and innovative therapies must be evaluated in clinical trials. Participation in a clinical trial may offer patients access to better treatments and advance the existing knowledge about treatment. Patients who are interested in participating in a clinical trial should discuss the risks and benefits with their physicians. Areas of active investigation aimed at improving the prevention and management of radiation side effects include:

Keratinocyte growth factor (KGF, palifermin) - This is a growth factor that has been shown to stimulate growth of epithelial cells, which make up the mucous membrane and line the mouth and throat. Keratinocyte growth factor is currently being tested in patients to prevent chemotherapy damage to the mucous membranes of the gastrointestinal tract.

Antioxidants - The antioxidant agent Cu/Zn superoxide dismutase (SOD) has shown promise in reducing early and late radiation-induced tissue injury. In one clinical trial, 448 patients with bladder cancer were randomly allocated to receive either SOD or a placebo after each radiation treatment. The patients who received SOD experienced fewer rectal problems and less bladder inflammation and skin toxicity.

Interleukin 11 - Interleukin 11 is a growth factor that is similar but not identical to what the body normally produces. Interleukin 11 has been approved by the FDA to stimulate platelet recovery in patients with low platelet counts as a result of chemotherapy. Clinical trials are currently under way to determine if Interleukin 11 will prevent side effects, especially in the mucous membranes and gastrointestinal tract, associated with chemotherapy and radiation therapy.

Prostaglandins - Prostaglandins are a group of compounds that affect the healing of inflammation and wounds. Misoprostol is a prostaglandin that is effective in treating complications that arise in patients with prostate cancer who receive radiation treatment. Inflammation of the rectum (radiation proctitis) is a known complication of radiation therapy in the treatment of prostate cancer.

Available medical treatment is usually ineffective and has focused on relieving symptoms after damage has occurred. One clinical study evaluated the effects of misoprostol in patients undergoing radiation therapy treatment for prostate cancer. In the study, nine patients received misoprostol rectal suppositories and seven patients received a placebo. The results indicated that misoprostol rectal suppositories significantly reduced acute and chronic radiation proctitis symptoms in patients receiving radiation therapy for prostate cancer.

This content was last reviewed August 15, 2010 by Dr. Reshma L. Mahtani.
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