Professional Drug Information > Amifostine

Amifostine (Systemic)

VA CLASSIFICATION
Primary: AN700

Commonly used brand name(s): Ethyol.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antineoplastic adjunct—

cytoprotective agent—

Indications

Accepted

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Nephrotoxicity, cisplatin-induced (prophylaxis)— Amifostine is indicated to reduce cumulative nephrotoxicity associated with cisplatin therapy ^{{01} {02} {03}} in patients with advanced ovarian carcinoma ^{{01} {03}}, non-small cell lung carcinoma (NSCLC) ^{{01} {03}}, or [advanced solid tumors of non-germ cell origin ^{02} .]

Xerostomia, radiation-induced (prophylaxis)—Amifostine is indicated to reduce the incidence of moderate to severe xerostomia associated with post-operative radiation treatment of head and neck cancer, where the radiation port includes a substantial portion of the parotid glands^{13}.

[Bone marrow toxicity, antineoplastic agent-induced (prophylaxis)]—Amifostine is indicated to reduce acute and cumulative hematologic toxicities associated with a cisplatin and cyclophosphamide (CP) regimen in patients with advanced solid tumors of non-germ cell origin. [Amifostine is also indicated to decrease bone marrow toxicity during treatment with high-dose cisplatin alone for head and neck carcinoma (Evidence rating: IIIC) ^{{04} {05}} , cyclophosphamide alone for malignant lymphoma (Evidence rating: IIIC) ^{{05} {06}} , carboplatin for NSCLC (Evidence rating: IIIC) ^{{05} {07}} , and carboplatin plus radiation therapy for head and neck carcinoma (Evidence rating: IIIC) ^{{05} {08}} .]¹

[Neurotoxicity, cisplatin-induced (prophylaxis)]¹—Amifostine is also indicated to decrease the frequency or severity of cisplatin-induced peripheral neuropathy ^{11} (Evidence rating: IC) and ototoxicity ^{{04} {11}} (Evidence rating: IC). ^{12}

Note: Because some animal data indicate a possible interference with antitumorigenic efficacy, use of amifostine in patients with potentially curable malignancies is not recommended ^{{01} {03}} except in the context of a clinical study ^{03}. However, amifostine did not interfere with the efficacy of a CP regimen for ovarian carcinoma ^{{02} {03}}, a cisplatin plus vinblastine regimen for non-small cell lung carcinoma ^{03}, or any of the other treatments mentioned above ^{{04} {06} {07} {08}}.


[Mucositis, radiation therapy or radiation combined with chemotherapy induced]¹—Amifostine is indicated to reduce the incidence of mucositis in patients receiving radiation therapy or radiation combined with chemotherapy.^{51}

[Myelodysplastic syndrome (treatment) ]¹—Amifostine may be used for salvage treatment, as part of a combination regimen (e.g., erythropoietin, topotecan, etoposide, cytarabine), for the treatment of myelodysplastic syndromes (MDS). There was not a clear consensus by the USP medical experts. Some of the experts are hesitant about the use of amifostine and suggest that individual case factors (e.g., International Prognostic Scoring System [IPSS] risk group, patient characteristics, etc.) be considered when choosing an appropriate treatment.^{{14}{15}{16}{17}{18}{19}{20}{31}{32}{33}{34}{35}{36}{37}{38}{39}{40}{41}{42}{43}{44}{45}{46}{47}{48}{49}}

Unaccepted
Amifostine should not be administered in patients receiving definitive radiotherapy, except in the context of a clinical trial, since there are insufficient data to exclude a tumor-protective effect in this setting. Although studies have been done, they were only with standard fractionated radiotherapy and only when less than or equal to 75% of both parotid glands were exposed to radiation. The effects of amifostine on the incidence of xerostomia and on toxicity in the setting of combined chemotherapy and radiotherapy and in the setting of accelerated and hyperfractionated therapy have not been systematically studied. ^{61}

¹ Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    214.23 ^{09}

Solubility
    Freely soluble in water ^{01}.

Mechanism of action/Effect:

Amifostine is a prodrug that is metabolized by alkaline phosphatase to an active free thiol metabolite. ^{{01} {02} {03}} The active thiol metabolite reduces cytotoxicity by binding to and detoxifying reactive metabolites of cisplatin ^{{01} {02} {03}} and alkylating agents ^{02} and by acting as a scavenger of free radicals ^{{01} {02} {03}} that may develop in tissues exposed to cisplatin or radiation ^{03}{13}. These actions occur more readily in normal tissue than in tumors because of the greater phosphatase activity, higher pH, and better vascularity in normal tissue ^{{01} {02} {03}}, resulting in selective protection of normal tissues ^{02}.

Distribution:

Measurable concentrations of the active free thiol metabolite have been found in bone marrow cells 5 to 8 minutes after intravenous administration. ^{{01} {02} {03}}

Biotransformation:

Amifostine is dephosphorylated by alkaline phosphatase in tissues primarily to the active free thiol metabolite and, subsequently, to a less active disulfide metabolite. ^{{01} {02} {03}}

Half-life:

Distribution—Less than 1 minute. ^{01}

Elimination—Approximately 8 minutes; less than 10% of amifostine remains in the plasma 6 minutes after drug administration.^{{61} {01}}

Elimination:
    Primarily via rapid metabolism and uptake into tissues. ^{02} Within 1 hour after infusion of 740 to 910 mg per square meter of body surface area (mg/m ² ) over 15 minutes ^{02} or rapid intravenous injection of 150 mg/m ² over 10 seconds ^{03}, urinary recovery of unchanged amifostine, the disulfide metabolite, and the thiol metabolite accounts for only 0.69%, 2.22%, and 2.64%, respectively, of the dose ^{{01} {02} {03}}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other aminothiol compounds also may be sensitive to amifostine. ^{{01} {02} {03}}

Carcinogenicity

Long-term animal studies to evaluate the carcinogenic potential of amifostine have not been done. ^{{01} {02} {03}} However, data from in vitro and in vivo studies indicate that amifostine may protect against the genotoxic effects of antineoplastic agents and the carcinogenic effects of radiation. ^{02}

Mutagenicity

Amifostine demonstrated no mutagenic effects in the Ames test and in the mouse micronucleus test. However, the free thiol metabolite demonstrated mutagenic effects in the Ames test and in in vitro mouse studies. This metabolite demonstrated no mutagenic effects in the mouse micronucleus test and did not demonstrate clastogenicity in human lymphocytes. ^{{01} {02} {03}} Data from in vitro and in vivo studies indicate that amifostine may protect against the mutagenic effects of chemotherapeutic agents. ^{02}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. ^{{01} {02} {03}} However, the potential risks associated with the antineoplastic agent(s) that the patient will also be receiving must be considered. It is usually recommended that use of antineoplastics, especially combination chemotherapy, be avoided whenever possible, especially during the first trimester. ^{10}

Amifostine is embryotoxic in rabbits at 60% of the recommended human dose based on body surface area. ^{{01} {03}} Amifostine also produces dose-dependent embryotoxicity, but not teratogenicity, in rats given doses higher than 200 mg per kg of body weight. ^{02}

FDA Pregnancy Category C. ^{{01} {03}}

Breast-feeding

It is not known whether amifostine ^{{01} {02} {03}} or its metabolites ^{03} are distributed into breast milk. However, because of the potential risks associated with the antineoplastic agent(s) that the patient will also be receiving, breast-feeding is not recommended during treatment.^{10}

Pediatrics

Although there is limited experience with amifostine in pediatric patients, appropriate studies on the relationship of age to the effects of amifostine have not been performed in the pediatric population. Safety, efficacy, and dosage have not been established. ^{03}


Geriatrics


Although there is limited experience with amifostine in patients older than 70 years of age ^{{02} {03}}, appropriate studies on the relationship of age to the effects of amifostine have not been performed in geriatric patients^{03}. The safety of amifostine administration has not been established in elderly patients.^{61}. However, since elderly patients are more likely to have age-related cardiovascular and cerebrovascular conditions, amifostine should be used with caution.^{{01} {02} {03}{61}{21}}

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Antihypertensives or
» Hypotension-producing medications, other (see Appendix II )    (amifostine may temporarily produce hypotension; antihypertensive or other potentially hypotension-producing medications should be discontinued 24 hours prior to amifostine administration; patients receiving antihypertensive therapy that cannot be discontinued temporarily should not receive amifostine ^{{01} {02} {03}})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Calcium, serum    (concentrations may be decreased; however, clinically significant hypocalcemia is rare ^{{01} {03}})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Cardiovascular conditions, preexisting, such as:
Arrhythmias or
Congestive heart failure or
Ischemic heart disease    (safety of amifostine has not been evaluated in patients with preexisting cardiovascular conditions ^{{01} {03}{61}})


Cerebrovascular conditions, preexisting, such as:
Stroke, history of, or
Transient ischemic attacks, history of    (safety of amifostine has not been evaluated in patients with preexisting cerebrovascular conditions ^{{01} {03}{61}})


» Dehydration or
» Hypotension    (amifostine may produce a temporary reduction in blood pressure; use of amifostine prior to correction of these conditions is not recommended ^{01}{02}{03}; use with caution in patients in whom hypotension may have serious consequences^{21}{61})


Hypocalcemia, predisposition to    (caution and careful monitoring of calcium concentrations are recommended in patients predisposed to hypocalcemia [e.g., patients with nephrotic syndrome ] ^{03})


» Hypersensitivity to aminothiol compounds ^{{01} {02} {03}}
Nausea or
Vomiting, predisposition to    (use with caution in patients in whom nausea and vomiting may have serious consequences; antiemetic medication should be administered prior to and in conjunction with amifostine, especially if therapy is in combination with highly emetogenic chemotherapy; carefully monitor fluid balance^{21}{61})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Blood pressure determinations    (recommended every 5 minutes during amifostine infusion ^{{01} {02} {03}}when administered for prophylaxis of chemotherapy-induced nephrotoxicity and at least before and immediately after the infusion when administered for prophylaxis of radiation-induced xerostomia^{13})


Calcium, serum    (recommended in patients at risk for developing hypocalcemia, e.g., those with nephrotic syndrome or those receiving multiple doses of amifostine^{{01} {02} {03}{61}})


Fluid balance    (monitoring recommended in patients receiving highly emetogenic chemotherapy ^{{01} {02} {03}})






Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Hypotension, asymptomatic ^{{01} {02} {03}}

Note: Hypotension usually occurs 14 minutes after the start of the infusion ^{{01} {02} {03}} and lasts 5 to 15 minutes ^{{01} {03}} (mean 6 minutes) ^{{01} {02} {03}}. Hypotension, usually brief systolic and diastolic, has been associated with one or more of the following: apnea, dyspnea, hypoxia, tachycardia, bradycardia, extrasystoles, chest pain, myocardial ischemia and convulsion. Rare cases of renal failure, myocardial infarction, respiratory and cardiac arrest have been observed during or after hypotension. ^{61}



Note: Allergic reactions characterized by one or more of the following manifestations have been observed during or after amifostine administration: hypotension, fever, chills/rigors, dyspnea, hypoxia, chest tightness, skin rashes, urticaria and laryngeal edema. Skin reactions including erythema multiforme, and in rare cases, Stevens-Johnson Syndrome and toxic epidermal necrolysis have occurred. Rare anaphylactoid reactions and cardiac arrest have been reported. In case of an acute allergic reaction, amifostine should be immediately and permanently discontinued.^{61}

Incidence rare
    
Allergic reactions ^{{01} {02} {03}} (chills; skin rash; sneezing)
    
atrial fibrillation/flutter (fast or irregular heartbeat; dizziness; fainting)— may sometimes be associated with hypotension or allergic reactions
    
seizures^{61} (convulsions; muscle spasm or jerking of all extremities; sudden loss of consciousness; loss of bladder control)
    
supraventricular tachycardia^{61} (fainting; fast, pounding, or irregular heartbeat or pulse; palpitations)—may sometimes be associated with hypotension or allergic reactions
    
Hypocalcemia ^{{01} {02} {03}} (burning or tingling sensation; muscle cramps)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Nausea and vomiting ^{{01} {02} {03}}

Note: Nausea and vomiting may be severe. ^{{01} {02} {03}} Administration of amifostine in addition to cisplatin plus cyclophosphamide increases the occurrence of nausea and vomiting on the day of infusion ^{{02} {03}}; in one clinical trial, the incidences of severe nausea and vomiting in amifostine-treated patients were almost double those in patients receiving only cisplatin plus cyclophosphamide. ^{03} However, amifostine did not increase the occurrence of delayed cisplatin-induced nausea and vomiting. ^{02}


Incidence less frequent or rare
    
fever^{61}
    
hypertension, transient^{61} (blurred vision ; dizziness; nervousness; headache; pounding in the ears; slow or fast heartbeat)
    
loss of consciousness, short term and reversible ^{61}
    
somnolence ^{{01} {02} {03}} (sleepiness, severe)
    
sneezing^{61}
    
syncope^{61} ( fainting)



Those not indicating need for medical attention
Incidence less frequent or rare
    
Dizziness ^{{01} {02} {03}}
    
feeling unusually warm ^{{01} {02} {03}} or cold ^{{01} {03}}
    
flushing or redness of face or neck ^{{01} {02} {03}}
    
hiccups ^{{01} {02} {03}}





Overdose
For more information on the management of overdose, contact a Poison Control Center (see Poison Control Center Listing)

Clinical effects of overdose
Although overdose has not been reported, the most likely symptom of amifostine overdose is hypotension. ^{01}{13}

At higher doses of amifostine, anxiety and reversible urinary retention have occurred.^{61}

Treatment of overdose
Treatment of hypotension includes infusion of 0.9% sodium chloride injection along with supportive treatment. ^{01}{13}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Amifostine (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to aminothiol compounds





Breast-feeding—Discontinuation of breast-feeding is recommended
Other medications, especially antihypertensives or hypotension-producing medications
Other medical problems, especially dehydration or hypotension

Proper use of this medication

» Proper dosing


Side/adverse effects
Signs of potential side effects, especially allergic reaction, atrial fibrillation, hypotension, hypocalcemia, seizures, and supraventricular tachycardia.


General Dosing Information
Amifostine should be administered as an intravenous infusion over a period of 15 minutes, beginning 30 minutes prior to chemotherapy. Longer infusion times are associated with a higher occurrence of side effects. ^{{01} {02} {03}}

Amifostine should be administered as an intravenous infusion over a period of 3 minutes, beginning 15 to 20 minutes prior to radiation therapy of the head and neck ^{13}.

Patients should be adequately hydrated prior to amifostine infusion^{13}.

Because amifostine may cause severe nausea and vomiting, patients should receive antiemetic therapy ^{{01} {02} {03}} that includes intravenous dexamethasone (20 mg) and a serotonin receptor antagonist before amifostine is administered. ^{{01} {03}} Other antiemetics may also be required, depending on the antineoplastic agents being given. ^{02}

Because amifostine may cause temporary hypotension, patients should be adequately hydrated before it is administered. ^{{01} {02} {03}} Patients should remain in the supine position, and their blood pressure should be monitored every 5 minutes during the infusion. ^{{01} {02} {03}}Despite adequate hydration and positioning of the patient, hypotension may occur during or shortly after amifostine administration. ^{61}

During and after amifostine infusion, care should be taken to monitor the blood pressure of patients whose antihypertensive medication has been interrupted since hypertension may be exacerbated by discontinuation of antihypertensive medication and other causes such as intravenous hydration. ^{61}

For treatment of adverse effects
If systolic blood pressure decreases significantly from baseline, it is recommended that the amifostine infusion be interrupted. A significant decrease is defined as:
   • Baseline systolic blood pressure (mm Hg) < 100—A reduction of 20 mm Hg. ^{{01} {02} {03}}
   • Baseline systolic blood pressure (mm Hg) 100 to 119—A reduction of 25 mm Hg. ^{{01} {02} {03}}
   • Baseline systolic blood pressure (mm Hg) 120 to 139—A reduction of 30 mm Hg. ^{{01} {02} {03}}
   • Baseline systolic blood pressure (mm Hg) 140 to 179—A reduction of 40 mm Hg. ^{{01} {02} {03}}
   • Baseline systolic blood pressure (mm Hg) ³ 180—A reduction of 50 mm Hg. ^{{01} {02} {03}}
Patients who require an interruption in the amifostine infusion should be placed in the Trendelenburg position and given an intravenous infusion of 0.9% sodium chloride injection through a separate line. ^{{01} {02} {03}} If blood pressure returns to normal within 5 minutes and the patient is asymptomatic, the infusion may be resumed and the full dose of amifostine administered. ^{{01} {03}} If the blood pressure does not return to normal, the amifostine dose for subsequent courses should be 740 mg per square meter of body surface area. ^{{01} {02} {03}{61}}

If clinically significant hypocalcemia occurs, administration of calcium supplements may be necessary. ^{{01} {02} {03}}

In the event of a serious allergic reaction such as anaphylaxis, epinephrine and other appropriate measures should be available for treatment. ^{61}


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to indications that are not included in U.S. product labeling.


AMIFOSTINE FOR INJECTION

Usual adult dose
Cisplatin-induced nephrotoxicity prophylaxis
[Antineoplastic agent-induced bone marrow toxicity prophylaxis]
[Cisplatin-induced neurotoxicity prophylaxis]¹
Intravenous infusion (over fifteen minutes), 910 mg per square meter of body surface area once a day, beginning thirty minutes prior to cisplatin chemotherapy. ^{{01} {02} {03}}

Note: If systolic blood pressure decreases significantly from baseline, it is recommended that the amifostine infusion be interrupted. If blood pressure returns to normal within five minutes and the patient is asymptomatic, the infusion may be resumed and the full dose of amifostine administered. If blood pressure does not return to normal, the dose for subsequent courses should be reduced to 740 mg per square meter of body surface area. ^{{01} {02} {03}}


Radiation-induced xerostomia prophylaxis
Intravenous infusion (over three minutes), 200 mg per square meter of body surface area once a day, beginning fifteen to thirty minutes prior to radiation therapy of the head and neck^{13}
[Mucositis, radiation therapy or radiation combined with chemotherapy induced]¹Intravenous infusion, 300 mg per square meter of body surface area once a day prior to radiation treatment.^{51}

[Myelodysplastic syndromes]¹
Patients have benefited from an intravenous bolus dose of 200 mg per square meter of body surface area (over 15 minutes), 3 times a week for 3 weeks, followed by a 2–week rest, in combination with other agents.^{20}


Usual adult prescribing limits
Doses larger than 1300 mg per square meter of body surface area per day have not been studied. ^{03}

Usual pediatric dose
Safety, efficacy, and dosage have not been established. ^{{01} {03}}

Size(s) usually available:
U.S.—


500 mg (anhydrous) single-dose vial (Rx) [Ethyol]

Canada—


500 mg (anhydrous) single-dose vial (Rx) [Ethyol]

Packaging and storage:
Store between 20 and 25 °C (68 and 77 °F). ^{03}

Preparation of dosage form:
Amifostine for injection is reconstituted by adding 9.7 mL of 0.9% sodium chloride injection, producing a solution containing 50 mg per mL. ^{03} The injection should be further diluted with additional 0.9% sodium chloride injection for administration by intravenous infusion. ^{01}

Stability:
After reconstitution, the amifostine injection is stable for up to 5 hours at room temperature (25 °C [77 °F]) ^{{01} {03}} and for up to 24 hours in the refrigerator (2 to 8 °C [36 to 46 °F]) ^{{01} {02} {03}}. After further dilution to a concentration of between 5 and 40 mg per mL, the amifostine injection, when stored in a polyvinyl chloride (PVC) bag, is stable for up to 5 hours at room temperature ^{{01} {03}} and for up to 24 hours in the refrigerator ^{{01} {02} {03}}. The reconstituted solution should not be used if it is turbid or contains a precipitate. ^{{01} {02} {03}}

Incompatibilities:
Amifostine for injection should not be mixed in solutions other than 0.9% sodium chloride injection or in 0.9% sodium chloride injections that contain other additives. ^{{01} {03}}

Developed: 06/29/1998
Revised: 03/07/2003

References

1. Ethyol package insert (Alza Pharmaceuticals—US), Rev 3/96, Rec 4/96.
   

2. Ethyol product information (Lilly—Canada). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 595-7.
   

3. Ethyol package insert (Alza Pharmaceuticals—US and U.S. Bioscience—US), Rev 12/97, Rec 4/6/98.
   

4. Planting AS, Veermorken JB, Catimel G, et al. Randomized Phase II study of weekly cisplatin with or without amifostine in patients with advanced head and neck cancer [abstract 887]. Proc Annu Meet Am Soc Clin Oncol 1996; 15: 314.
   

5. Reviewers' responses to Question #2, monograph draft 5/98.
   

6. Aviles A, Diaz-Maqueo JC, Talavera A, et al. Bone marrow protection with amifostine in the treatment of high-risk malignant lymphoma. Eur J Cancer 1997; 33: 1323-5.
   

7. Mercer V, Anderson H, Habboubi N, et al. A phase III randomized study of carboplatin and amifostine versus carboplatin and G-CSF in patients with inoperable non-small cell lung cancer (NSCLC) [abstract 1708]. Proc Annu Meet Am Soc Clin Oncol 1997; 16: 474a.
   

8. Buntzel J, Kuttner K, Russell L, et al. Selective cytoprotection by amifostine in the treatment of head and neck cancer with simultaneous radiochemotherapy [abstract 1400]. Proc Annu Meet Am Soc Clin Oncol 1997; 16: 393a.
   

9. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: United States Pharmacopeial Convention Inc; 1997. p. 46.
   

10. Standard precaution approved by Panel consensus for all antineoplastic agents.
    

11. Kemp G, Rose P, Lurain J, et al. Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol 1996; 14: 2101-12.
    

12. Reviewers' responses to Question #3, monograph draft 5/98.
    

13. Ethyol package insert (Alza Pharmaceuticals—US and U.S. Bioscience—US), Rev 6/99, Rec 9/99.
    

14. Invernizzi R, Pecci A, Travaglino E, et al. Clinical and biological effects of treatment with amifostine in myelodysplastic syndromes. Br J Haematol 2002; 118 (1): 246-50.
    

15. Garcia-Manero G, Faderl S, Giles F, et al. A phase I study of idarubicin dose escalation with amifostine and high-dose cytarabine in patients with relapsed acute myelogenous leukemia and myelodysplastic syndromes. Haematologica 2002 Aug; 87(8): 804-7.
    

16. Neumeister P, Jaeger G, Eibl M, et al. Amifostine in combination with erythropoietin and G-CSF promotes multilineage hematopoiesis in patients with myelodysplastic syndrome. Leuk Lymphoma 2001 Jan; 40(3-4): 345-9.
    

17. Galanopoulos A, Kritikou-Griva E, Gligori J, et al. Treatment of patients with myelodysplastic syndrome with amifostine. Leuk Res 2001 Aug; 25(8): 665-71.
    

18. Preisler HD, Venugopal P, Gregory SA, et al. Poor prognosis acute myelogenous leukemia: 1 - response to treatment with high dose cytarabine/mitoxantrone/ethyol @ (Amifostine). Leuk Res 2000 Aug; 24 (8): 671-80.
    

19. Hofmann WK, Seipelt G, Ottmann OG, et al. Effect of treatment with amifostine used as a single agent in patients with refractory anemia on clinical outcome and serum tumor necrosis factor alpha levels. Ann Hematol 2000 May; 79(5): 255-8.
    

20. Reviewers' consensus on the reconsideration of amifostine for the treatment of myelodysplastic syndromes evidence table, 2/22/03.
    

21. Expert Committee comment, 2/19/03.
    

22. Not used.
    

23. Not used.
    

24. Not used.
    

25. Not used.
    

26. Not used.
    

27. Not used.
    

28. Not used.
    

29. Not used.
    

30. Not used.
    

31. Yilmaz A, Kaufmann CC, Binder C, et al. Effects of amifostine in a patient with an advanced-stage myelodysplastic syndrome. Ann Hematol 2001; 80(1): 53-7.
    

32. Tefferi A, Elliott MA, Steensma DP, et al. Amifostine alone and in combination with erythropoietin for the treatment of favorable myelodysplastic syndrome. Leuk Res 2001; 25(2): 183-5.
    

33. Grossi A, Fabbri A, Santini V, et al. Amifostine in the treatment of low-risk myelodysplastic syndromes. Haematologica 2000; 85(4): 367-71.
    

34. Raza A, Qawi H, Lisak L, et al. Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone. Blood 2000; 95(5): 1580-7.
    

35. Haase D, Schanz J, Gassmann W, et al. Amifostine long-term application vs. supportive care - a multicentric phase iii trial in patients with low-risk MDS (IPSS<1.5). 42nd annual meeting the American Society of Hematology. December 1-5, 2000; San Francisco, CA: [Abst 4859].
    

36. Fung HC, Bhatia R, O'Donnell M, et al. Amifostine (Ethyol) in combination with topotecan and Ara-C for patients with poor risk myelodysplasia (MDS) and secondary acute myelogenous leukemia. 42nd annual meeting the American Society of Hematology. December 1-5, 2000; San Francisco, CA: [Abst 4858].
    

37. Musto P, Grossi A, Balestri F, et al. Association of amifostine and erythropoietin for the treatment of anemia in myelodysplastic syndromes. 42nd annual meeting the American Society of Hematology. December 1-5, 2000; San Francisco, CA: [Abst 4866].
    

38. Auletta JJ, Shurin S. Improved hematopoiesis using amifostine in secondary myelodysplasia. J Pediatr Hematol Oncol 1999; 21(6): 531-4.
    

39. Bourantas KL, Tsiara S, Kapsali E, et al. Treatment of patients with myelodysplastic syndromes with amifostine. Leuk Res 1999; 23 (Suppl 1): S78 [Abst 205].
    

40. De Castro CM, Gockerman JP, Moore JO, et al. Treatment of myelodysplastic syndrome (MDS) with amifostine. Leuk Res 1999; 23 (Suppl 1): S77 [Abst 204].
    

41. Nair R, Nair CN, Advani SH, et al. Role of amifostine in patients with aggressive myelodysplastic syndromes. Leuk Res 1999; 23 (Suppl 1): S78 [Abst 206].
    

42. Larsen SR, Manoharan A. Amifostine in the treatment of patients with myelodysplastic syndrome. Aust N Z J Med 1999; 29(5): 753-4.
    

43. Neumeister P, Jäger G, Schmidt HH, et al. Amifostine in combination with erythropoietin and G-CSF promotes multilineage hematopoiesis in patients with myelodysplastic syndrome (MDS) -a pilot study. Leuk Res 1999; 23 (Suppl 1): S78 [Abst 208].
    

44. Rosenthal CJ, Thapper A. Sequential therapy with amifostine, topotecan, and etoposide induced repeated responses in patients with myelodysplastic syndrome. Leuk Res 1999; 23 (Suppl 1): S77 [Abst 203].
    

45. Weber BE, Köchling G, Stöckl E, et al. Successful treatment of myelodysplastic syndromes with amifostine. Ann Hematol 1998; 77 (Suppl 2): S58 [Abst 227].
    

46. Bowen DT, Denzlinger C, Brugger W, et al. Poor response rate to a continuous schedule of Amifostine therapy for 'low/intermediate risk' myelodysplastic patients. Br J Haematol 1998; 103(3): 785-7.
    

47. Buresh CM, Baker KS, Shafer M. Fever and rash after amifostine therapy. J Pediatr Hematol Oncol 1998; 20(4): 361-2.
    

48. Fetscher S, Mertelsmann R. Supportive care in hematologic malignancies. Curr Opin Hematol 1998; 5(4): 271-86.
    

49. Jarchum G, Ryser R, Bove V, et al. Treatment of myelodysplastic syndromes (MDS) with amifostine (AMF). Blood 1997; 90(10 Suppl): 288b [Abst 4041].
    

50. Not used.
    

51. Reviewers' concensus on ballot of 04/08/2002.
    

52. Buntzel J, Kuttner K, Frohlich D, Glatzel M. Selective cytoprotection with amifostine in concurrent radiochemotherapy for head and neck cancer. Ann Oncol 1998 May; 9(5):505-9.
    

53. Koukourakis MI, Kyrias G, Kakolyris S, Kouroussis C, Frangiadaki C, Giatromanolaki A, Retalis G, Georgoulias V. Subcutaneous administration of amifostine during fractionated radiotherapy: a randomized phase II study. J Clin Oncol 2000 Jun; 18(11):2226-33.
    

54. Dunst J, Semlin S, Pigorsch S, Muller AC, Reese T. Intermittent use of amifostine during postoperative radiochemotherapy and acute toxicity in rectal cancer patients. Strahlenther Onkol 2000 Sep; 176(9):416-21.
    

55. De Souza CA, Santini G, Marino G, Nati S, Congiu AM, Vigorito AC, Damasio E. Amifostine (WR-2721), a cytoprotective agent during high-dose cyclophosphamide treatment of non-Hodgkin's lymphomas: a phase II study. Braz J Med Biol Res 2000 Jul; 33(7):791-8.
    

56. Brizel DM, Wasserman TH, Henke M, Strnad V, Rudat V, Monnier A, Eschwege F, Zhang J, Russell L, Oster W, Sauer R. Phase III randomized trial of amifostine as a radioprotector in head and neck cancer. J Clin Oncol 2000 Oct 1;18(19):3339-45.
    

57. Bourhis J, De Crevoisier R, Abdulkarim B, Deutsch E, Lusinchi A, Luboinski B, Wibault P, Eschwege F. A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2000 Mar 15;46(5):1105-8.
    

58. Antonadou D, Coliarakis N, Synodinou M, Athanassiou H, Kouveli A, Verigos C, Georgakopoulos G, Panoussaki K, Karageorgis P, Throuvalas N. Randomized phase III trial of radiation treatment+/- amifostine in patients with advanced-stage lung cancer. Int J Radiat Oncol Biol Phys 2001 Nov 15;51(4):915-22.
    

59. Bennett CL, Lane D, Stinson T, Glatzel M, Buntzel J. Economic analysis of amifostine as adjunctive support for patients with advanced head and neck cancer: preliminary results from a randomized phase II clinical trial from Germany. Cancer Invest 2001;19(2):107-13.
    

60. Werner-Wasik M, Axelrod RS, Friedland DP et al. Preliminary report on reduction of esophagitis by amifostine in patients with non-small cell lung cancer treated with chemoradiaiton. Clin Lung Cancer 2001;2(4): 284-289.
    

61. Product Information: Ethyol®, amifostine. MedImmune Oncology, Gaithersburg, MD, (PI revised 10/2001) reviewed 11/2002