Amifostine is a cytoprotective agent that can protect DNA and RNA from damage from chemotherapeutic agents that involve binding to DNA, such as platinum containing alkylating agents. It may also accelerate DNA repair and protect cells against harmful effects of radiation treatment. Amifostine is administered intravenously. Amifostine has been studied for its effects on diarrhea, mucositis, and peripheral neuropathy.
Bensadoun, R.J., Schubert, M.M., Lalla, R.V., & Keefe, D. (2006). Amifostine in the management of radiation-induced and chemo-induced mucositis. Supportive Care in Cancer, 14, 566–572.
DATABASES USED: MEDLINE (May 2002–May 2005), selected studies related to amifostine
KEYWORDS: stomatitis, mucous membrane, mucositis (text in titles and abstracts)
INCLUSION CRITERIA: Limited to \"neoplasm\" and English language
FINAL NUMBER STUDIES INCLUDED = 29 trials included, 6 covered in detail; pilot studies and randomized, controlled studies included
SAMPLE RANGE ACROSS STUDIES: Sample sizes range from small to more than 200
KEY SAMPLE CHARACTERISTICS: Patients with head and neck cancer receiving radiation alone; patients with cancers of various origin receiving combination chemoradiation or radiation alone; patients receiving intensity-modulated radiation therapy; and studies examining routes of administration in patients with head and neck cancer, patients with prostate cancer, and patients receiving epirubicin
The study did not provide sufficient evidence for recommendations related to amifostine and prevention or management of oral mucositis. The authors recommended maintaining the original guideline from the Multinational Association of Supportive Care in Cancer—chemoradiation for non-small cell lung cancer for prevention of esophagitis (level of evidence III, grade of recommendation C). Several small studies demonstrated prevention of proctitis in patients with only rectal carcinoma. No effect was shown for other pelvic cancers. Therefore, the authors suggested that the guideline be revised to include the recommendation of amifostine at least 340 mg/m2 IV daily prior to radiation (level of evidence III, grade of recommendation B) for rectal carcinoma to prevent proctitis. For patients with hematologic disorders, no significant data could reinforce any recommendations. Possible future uses and routes of amifostine also were discussed.
Nicolatou-Galitis, O., Sarri, T., Bowen, J., Di Palma, M., Kouloulias, V.E., Niscola, P., . . . Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of amifostine for the management of oral mucositis in cancer patients. Supportive Care in Cancer, 21(1), 357–364.
STUDY PURPOSE: To review available literature from 1966 to December 31, 2010 to define clinical practice guidelines for the use of amifostine for prevention and treatment of oral mucositis in patients with cancer
TYPE OF STUDY: Systematic review
DATABASES USED: MEDLINE
KEYWORDS: Extensive list provided (anti-inflammatory agents) including amifostine, antitumor necrosis factor (TNF), non-steroidal anti-inflammatory drugs, TNF inhibitor, etc.
INCLUSION CRITERIA: Detailed information is provided in a different section of the journal. Studies relevant to the management of radiation and/or chemotherapy-induced oral mucositis using anti-inflammatory interventions including amifostine
EXCLUSION CRITERIA: Articles that did not report on intervention and mucositis outcomes, animal or in vitro studies, non-English articles, methodologic quality, and anti-inflammatory agents other than amifostine
TOTAL REFERENCES RETRIEVED: 908
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Only articles that investigated amifostine specifically were selected. Levels of evidence were based on the Somerfield criteria, and study methodology was evaluated on the Hadorn criteria. These were integrated into guideline categories—recommendation, suggestion, or no guideline possible.
PHASE OF CARE: Active antitumor treatment
No guideline, suggestion, or recommendation for mucositis prevention with amifostine was possible in any of the following groupings.
Conflicting results, insufficient data, and major Hadorn flaws did not allow any guideline related to the use of amifostine for oral mucositis prevention. New well-designed trials are necessary that include timing of amifostine infusion prior to radiotherapy, consistent dose of amifostine, and cancer therapy intensity and modality.
Too many studies may have been eliminated up front.
Because no guidelines are recommended by this review, nurses who continue to administer amifostine for mucositis prevention carefully should document the results and look for ways to participate in well-designed trials. Nurses may consider advocating against the use of amifostine outside of research until guidelines can be established for its use.
Antonadou, D., Pepelassi, M., Synodinou, M., Puglisi, M., & Throuvalas, N. (2002). Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer. International Journal of Radiation Oncology, Biology, Physics, 52, 739–747.
Patients in the study group received 300 mg/m2 amifostine 15–30 minutes before radiation therapy (RT) on days 1–5 of each week. Patients in both the study group and the control group received 90 mg/m2 carboplatin once per week before RT. Treating physicians and patients reported data.
The study was conducted between January 1997 and January 1998.
The Radiation Therapy Oncology Group/ European Organization for Research and Treatment of Cancer (RTOG/EORTC) 0–4 grading system was used.
Buentzel, J., Micke, O., Adamietz, I.A., Monnier, A., Glatzel, M., & deVries, A. (2006). Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: A randomized placebo-controlled phase III study. International Journal of Radiation Oncology, Biology, Physics, 64, 684–691.
To evaluate the efficacy and safety of IV amifostine during radiochemotherapy for head-and-neck cancer
Patients in the study group received 300 mg/m2 IV amifostine on the days in which they received carboplatin and radiation therapy (RT). On the days in which they received only RT, they were given 200 mg/m2 IV amifostine.
The study was conducted between October 1996 and October 1999.
The intervention was not found to be effective in the management of mucositis toxicity.
This was the first randomized and placebo-controlled study of amifostine in the head and neck cancer population.
Hwang, W.Y., Koh, L.P., Ng, H.J., Tan, P.H., Chuah, C.T., Fook, S.C., … Goh, Y.-T. (2004). A randomized trial of amifostine as a cytoprotectant for patients receiving myeloablative therapy for allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplantation, 34, 51–56.
Patients were given 1,000 mg/day IV amifostine (740 mg/m2) once a day or divided (depending on frequency of chemotherapy or total body irradiation [TBI]), rounded to nearest 500 mg, and given over 15 minutes prior to chemotherapy or TBI.
This was a single-institution, randomized, open-label trial conducted between August 1998 and October 2003.
The World Health Organization (WHO) Mucositis grading scale was used daily during the study, followed by the Common Toxicity Criteria in Cancer Therapy Evaluation Program (CTEP).
Jantunen, E., Kuittinen, T., & Nousiainen, T. (2002). A pilot study on feasibility and efficacy of amifostine preceding high-dose melphalan with autologous stem cell support in myeloma patients. Leukemia and Lymphoma, 43, 1961–1965.
The study was conducted between November 1998 and February 2000.
This was a pilot, feasibility study.
The National Cancer Institute (NCI) Common Toxicity Criteria for Oral Mucositis was used to assess oral mucositis daily.
Most of the patients (9 out of 10) received the full dose of amifostine. One patient received only 780 mg/m2 because of recurrent hypotension. Significant nausea, as well as hypotension and vomiting, occurred.
Amifostine did not show a benefit for gastrointestinal toxicity or mucositis of more than grade 2.
Lorusso, D., Ferrandina, G., Greffi, S., Gadducci, A., Pignata, S., Tateo, S. … Scambia, G. (2003). Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients. Annals of Oncology, 14, 1086–1093.
Patients receiving carboplatin (area under the curve [AUC] 5 mg per minute/ml) and 175 mg/m2 paclitaxel were randomly assigned to receive 910 mg/m2 IV amifostine 30 minutes prior to carboplatin.
The study was conducted between April 1999 and July 2001.
This was a phase III, multicenter, randomized trial.
A significant difference was found in grade 3-4 mucositis (4.7% in the amifostine group versus 15.4% in the control group, p < 0.0001).
Spencer, A., Horvath, N., Gibson, J., Prince, H.M., Herrmann, R., Bashford, J., … Taylor, K. (2005). Prospective randomized trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation. Bone Marrow Transplantation, 35, 971–977.
Patients in the study group received 910 mg/m2 IV amifostine 15–30 minutes prior to 200 mg/m2 melphalan prior to autotransplant for multiple myeloma (MM).
This was a multicenter study conducted between May 1999 and November 2000.
This was an open label, randomized study.
The World Health Organization (WHO) scale for mucositis, median duration of mucositis, duration of total parenteral nutrition (TPN), and duration of narcotics use were recorded.
This study provided weak statistical evidence for the use of amifostine.
Thieblemont, V.C., Dumontet, C., Saad, H., Roch, N., Bouafia, F., Arnaud, P., … Coiffier, B. (2002). Amifostine reduces mucosal damage after high-dose melphalan conditioning and autologous peripheral blood progenitor cell transplantation for patients with multiple myeloma. Bone Marrow Transplantation, 30, 769–775.
Patients in the study group received 740 mg/m2 IV amifostine prior to 200 mg/m2 melphalan.
This study was conducted betwen September 1999 and December 2001.
This was a prospective, comparative, non-randomized controlled, phase 2 trial conducted at a single institution.
Gibson, R.J., Keefe, D.M., Lalla, R.V., Bateman, E., Blijlevens, N., Fijlstra, M., … Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of agents for the management of gastrointestinal mucositis in cancer patients. Supportive Care in Cancer, 21(1), 313–326.
To systematically review current evidence for prevention and treatment of gastrointestinal (GI) mucositis in adults and children receiving cancer treatment and to update relevant Multinational Association of Supportive Care in Cancer (MASCC) guidelines
This was an evidence-based guideline developed based on a systematic review of the literature with rating of levels of evidence and identification of study flaws.
Database searched was MEDLINE.
Search keywords were numerous and included all known possible interventions tested.
Inclusion and exclusion criteria were not stated in this article but provided elsewhere in the journal.
A total of 1,336 papers were initially retrieved; of these, 146 were reviewed for development of the guidelines.
This review had a limited search strategy, as only one database was searched. In addition, most of the suggestions and recommendations provided were based on low-level evidence by the rating system used.
These guidelines provide some suggestions for management of oral mucositis and diarrhea in patients with cancer. They also provide information regarding evidence for mucositis in the entire GI tract.