Ethyol (amifostine) - 2 indications

Scroll down for information on each indication:

• to reduce cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer; approved December 1995
• to reduce xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer; approved June 1999

General Information

Ethyol (amifostine) is a cytoprotective agent. 

Ethyol is specifically indicated for the following:

• reduction of cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer. 
• reduction of the incidence of moderate to severe xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands.

Ethyol is supplied as a solution for intravenous infusion. Scroll down to see the recommended dosing/administration for each therapeutic indication.

Mechanism of Action

Ethyol (amifostine) is a prodrug that is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite. This metabolite is believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. The ability of Ethyol to differentially protect normal tissues is attributed to the higher capillary alkaline phosphatase activity, higher pH and better vascularity of normal tissues relative to tumor tissue, which results in a more rapid generation of the active thiol metabolite as well as a higher rate constant for uptake into cells. The higher concentration of the thiol metabolite in normal tissues is available to bind to, and thereby detoxify, reactive metabolites of cisplatin. This thiol metabolite can also scavenge reactive oxygen species generated by exposure to either cisplatin or radiation.

Side Effects 

Adverse effects associated with the use of Ethyol may include, but are not limited to, the following:

• hypotension
• nausea
• vomiting

Indication 1 - cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer

approved December 1995

Dosing/Administration

The recommended starting dose of Ethyol is 910 mg/m2 administered as a 15-minute intravenous infusion, starting 30 minutes prior to chemotherapy. Do not exceed a 15-minute infusion time due to the increased risk of infusion-related reactions. The use of less than 15-minute infusion times for Ethyol use with chemotherapy have not been established.

Clinical Trial Results

A randomized controlled trial compared six cycles of cyclophosphamide 1000 mg/m2, and cisplatin 100 mg/m2 with or without Ethyol pretreatment at 910 mg/m2, in two successive cohorts with a total of 242 patients with advanced ovarian cancer. In both cohorts, after multiple cycles of chemotherapy, pretreatment with Ethyol significantly reduced the cumulative renal toxicity associated with cisplatin, as assessed by the proportion of patients who had ≥40% decrease in creatinine clearance from pretreatment values, protracted elevations in serum creatinine (>1.5 mg/dL), or severe hypomagnesemia.

Indication 2 - to reduce xerostomia in patients undergoing post-operative radiation treatment for head and neck cancer

approved June 1999

Dosing/Administration

The recommended dose of Ethyol is 200 mg/m2 administered as a 3-minute intravenous infusion, starting 15-30 minutes prior to standard fraction radiation therapy (1.8-2.0 Gy).

Clinical Trial Results

A randomized controlled trial  of standard fractionated radiation (1.8 Gy - 2.0 Gy/day for 5 days/week for 5-7 weeks) with or without Ethyol, administered at 200 mg/m2 as a 3 minute intravenous infusion 15‑30 minutes prior to each fraction of radiation, was conducted in 315 patients with head and neck cancer. Patients were required to have at least 75% of both parotid glands in the radiation field. The incidence of Grade 2 or higher acute (90 days or less from start of radiation) and late xerostomia (9‑12 months following radiation) as assessed by RTOG Acute and Late Morbidity Scoring Criteria, was significantly reduced in patients receiving Ethyol. 

At one year following radiation, whole saliva collection following radiation showed that more patients given Ethyol produced >0.1 gm of saliva (72% vs. 49%). In addition, the median saliva production at one year was higher in those patients who received Ethyol (0.26 gm vs. 0.1 gm). Stimulated saliva collections did not show a difference between treatment arms. These improvements in saliva production were supported by the patients' subjective responses to a questionnaire regarding oral dryness.