Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Ethyol (Schering-Plough)
vials containing 500 mg as lyophilised powder
Indication: chemo protection
As the drugs used in chemotherapy damage normal tissues as well as cancer cells, their dose may be limited by toxicity. Amifostine has been developed to protect the kidney from nephrotoxic effects and to prevent the complications of haematologicaltoxicity.
The drug is given by a 15 minute infusion starting half an hour before chemotherapy. Amifostine is rapidly converted to its active metabolite by alkaline phosphatase. As the concentration of this enzyme is higher in normal cells, only small amounts of the metabolite occur in tumour cells. The metabolite may protect normal cells by scavenging the free radicals produced during chemotherapy.
Amifostine has been approved for decreasing the incidence of the acute and cumulative nephrotoxicity associated with platinum-based therapy. It is also indicated to decrease the incidence of neutropenia-related fever and infection induced by DNA-binding agents (classical alkylating agents such as cyclophosphamide and non-classical alkylating agents such as mitomycin-C and platinum-containing drugs).
As most of the drug and its metabolites are taken into the tissues, very little is excreted. The active metabolite can be found in bone marrow within 10 minutes of the infusion.
In advanced ovarian cancer, amifostine, compared to chemotherapy alone, reduces the incidence of myelotoxicity. The patients given amifostine also spent fewer days in hospital for the treatment of complications of neutropenia.
Although amifostine appears to have some benefit in preventing adverse effects, it has its own adverse reactions. Hypotension commonly occurs towards the end of the infusion. Although the hypotension is transient, some patients may become unconscious or require the infusion to be stopped. Nausea and vomiting also occur frequently. Giving the infusion more slowly increases the adverse effects. Calcium concentrations should be measured as they can be reduced by amifostine.
