Amifostine (Ethyol) as a Potential Radioprotectant

July 15, 2009 - 12:33 pm email to a friend

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Dr Mehta

Amifostine is the generic name for a drug that is marketed using the name Ethyol. This medicine is supposed to protect against the damaging effects of radiation. The medicine was originally developed by the military that was working on a medicine that would protect soldiers from exposure from a radioactive “dirty” bomb. It was ultimately licensed by the pharmaceutical industry for medical uses.

The drug is supposed to be a free radical scavenger. Since radiation creates free radicals that subsequently damage DNA, a free radical scavenger would theorectically mitigate some of this effect. The drug is believed to be preferentially taken up by normal tissues instead of the tumor, which is why amifostine shouldn’t protect the tumor.

Amifostine was initially studied in patients receiving radiation for primary cancers of the head and neck. The early studies demonstrated that patients receiving this drug were more likely to preserve salivary function than patients not receiving this drug. The explanation was that the drug was taken up by the normal parotid gland in patients. The parotid gland, located in the cheek, produces a large amount of our normal saliva. Since patients receiving the drug seemed to have more saliva after treatment, the thought was that this agent must have “protected” the parotid gland in at least some patients.

Importantly, however, when that study was enrolling patients, the radiation techniques were older and exposed the entire parotid gland to the full dose of radiation. Today, most patients with head and neck cancer receive IMRT (intensity modulated radiotherapy), which is able to avoid the parotid gland while still delivering radiation to the target tissues in the region. Most patients receiving newer radiotherapy techniques are able to maintain their salivary function post treatment.

When the drug was originally approved by the FDA, it was administered as an IV infusion. The IV administration of this drug was associated with several side effects, including nausea/vomiting and low blood pressure (hypotension). The drug needs to be administered just before the radiation is delivered to have its most effect (at least theorectically). Recently, the drug has been administered as a subcutaneous (under the skin) injection. This form of administration is not FDA approved but has been adopted by many centers. This method is associated with skin rash/reaction, less nausea/vomiting, and much less hypotension. Overall, then, this drug is somewhat difficult to administer because patients have these side effects. It is important to keep patients well hydrated and premedicated if you are going to give the drug.

There has been a lot of interest in determining whether this drug protects the mucosa (the inner lining of the mouth and the esophagus) as well. Unfortunately, the data are not convincing that this drug protects the mucosa. In some studies, there is a small suggestion that some patients may experience either less intense mucositis, less duration of mucositis, or quicker recovery. In most studies, a positive benefit was not seen in terms of mucositis protection.

The drug has been studied in combination with radiotherapy or chemotherapy and radiation in the setting of lung cancer by several groups, including our own. In a small study at MD Anderson Cancer Center, there appeared to be a benefit in terms of reducing pulmonary toxicity when patients received the drug. This study evaluated twice a day radiation and concurrent chemotherapy in non small cell carcinoma, a regimen that is not widely used. In a large RTOG study, this drug failed to show a benefit in the setting of induction chemotherapy followed by concurrent chemoradiotherapy. Consequently, most physicians don’t use this drug in the setting of treatment for non small cell lung cancer.

I think that most practicing physicians wish that this agent had been better studied. Most of the studies that failed to show a benefit could have been designed better, and perhapsmore carefully designed trials might have teased out which patients would benefit from this agent. Unfortunately, we are left with the data that we have. I have used this agent in very few of my patients with lung cancer.

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