• Systemic Treatment Disease Site Group. Vincent M, Bramwell V, Moran LA, Anderson D. Use of amifostine to ameliorate the toxic effects of chemotherapy in the treatment of cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2003 Jan [online update]. 19 p. (Practice guideline; no. 12-6). [27 references]

In the treatment of patients with non-leukemic cancer, with conventional doses of alkylating agents and/or moderate or higher doses of cisplatin, the use of amifostine should be guided by the following considerations:

• In patients scheduled to receive high per cycle doses of cisplatin (>100 mg/m²) or high cumulative doses (>600 mg/m²), amifostine is a reasonable therapeutic option to reduce the incidence and severity of neurotoxicity, ototoxicity or clinically relevant nephrotoxicity. There are currently no data to determine whether amifostine produces similar benefits at lower per cycle doses or cumulative doses of cisplatin. However, the incidence of neurotoxicity is predicted to rise at cumulative doses of cisplatin (>300 mg/m²) and the use of amifostine could be considered in this setting.
• Amifostine is one of several reasonable therapeutic options to reduce myelosuppression. In assessing the effects of amifostine on quality of life, particularly when amifostine is used as part of palliative treatment, acute toxic effects of amifostine, such as nausea and vomiting and hypotension, need to be weighed against its ability (based on one randomized study) to reduce the morbidity of myelosuppression (episodes of neutropenic fever).
• If the objective of treatment with amifostine is to improve survival by means of dose maintenance of chemotherapy, there is no evidence to justify the routine use of amifostine.

Note: Amifostine has been investigated with only a limited number of cytotoxic agents apart from the alkylating agents and platinum analogues. One of these is paclitaxel, for which there is conflicting evidence regarding a pharmacokinetic interaction with amifostine. Evidence from a randomized phase II trial suggests that amifostine does not provide protection from any of the toxicities (including neurotoxicity) of single-agent paclitaxel, despite preclinical evidence that a selective cytoprotective effect for normal cells might exist. This finding is not surprising, given the absence of any plausible biochemical explanation for a protective effect (apart from a pharmacokinetic one) and given the mechanism of action of the taxane. However, the trial indicated no tumour-protective effect either and amifostine should be further investigated as a cytoprotectant in platinum-taxane combinations.

None provided

1998 Guideline
Five randomized controlled trials were identified which evaluated the effects of amifostine on chemotherapy-induced toxicities: 4 compared chemotherapy plus amifostine with chemotherapy alone, and 1 trial compared chemotherapy plus amifostine with chemotherapy plus granulocyte-colony stimulating factor (G-CSF). Four trials used platinum-based regimens in patients with a variety of malignancies, and one trial used mitomycin-C in patients with colorectal adenocarcinoma. Only one trial involved more than 100 patients, and this trial also reported the effects of treatment on neurotoxicity, ototoxicity and nephrotoxicity.

2003 Update
One practice guideline was located in the literature update searches. The guideline, developed by the American Society of Clinical Oncology, was based on the same evidence as the current guideline produced by the Practice Guidelines Initiative (PGI). Appendix 2 of the original guideline document contains a comparison between the PGI guideline and the American Society of Clinical Oncology guideline.

Eight randomized controlled trials that met the eligibility criteria were located in literature update searches. None of these trials were placebo-controlled. These trials have been added to Tables 1 and 2 of the original guideline document. Five trials reported hematologic toxic effects using various outcome measures. Four trials reported on nephrotoxicity outcomes and four trials reported on neurotoxicity outcomes including ototoxicity. Survival and/or tumour response data were available from five trial reports. Quality of life was not assessed in any of the new trials.

• Systemic Treatment Disease Site Group. Vincent M, Bramwell V, Moran LA, Anderson D. Use of amifostine to ameliorate the toxic effects of chemotherapy in the treatment of cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2003 Jan [online update]. 19 p. (Practice guideline; no. 12-6). [27 references]

Not applicable: The guideline was not adapted from another source.

1998 Dec 18 (updated online 2003 Jan)

Program in Evidence-based Care - State/Local Government Agency [Non-U.S.]

The Practice Guidelines Initiative (PGI) is the main project of the Program in Evidence-based Care (PEBC), a Province of Ontario initiative sponsored by Cancer Care Ontario and the Ontario Ministry of Health and Long-Term Care.

Cancer Care Ontario, Ontario Ministry of Health and Long-Term Care

Provincial Systemic Treatment Disease Site Group (STDSG)

Members of the Systemic Treatment Disease Site Group disclosed potential conflict of interest information.

None available

This summary was completed by ECRI on August 19, 1999. The information was verified by the guideline developer as of September 17, 1999. This NGC summary was updated by ECRI on December 14, 2001 and most recently on July 21, 2003. The most recent information was verified by the guideline developer as of August 6, 2003.