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.
Tomudex (ICI Pharmaceuticals)
vials containing 2 mg as lyophilised powder
Indication: colorectal cancer
Thymidylate synthetase is an enzyme involved in the synthesis of DNA. Anticancerdrugs such as methotrexate and fluorouracil (5FU) have an effect on the enzyme, but raltitrexed is a more specific inhibitor. Inhibition of thymidylate synthetase leads to cell death.
Raltitrexed has been studied in patients with advanced colorectal cancer. It is given by infusion every 3 weeks, in the absence of toxicity. Half of a radio labelled dose will not be recovered, suggesting that some raltitrexed is retained in the tissues. Traces of the radiolabel can still be found in red blood cells 29 days after an infusion. The drug is mainly excreted unchanged in the urine so the dose is modified if renal function is reduced. Serum creatinine should be measured before each treatment.
Many of the patients experience adverse reactions. The most common adverse effects are gastrointestinal, including diarrhoea, anorexia, nausea and vomiting. Blood counts and liver function should be tested before each treatment, because raltitrexed can cause leucopenia, anaemia and increased liver enzyme concentrations. Other adverse effects include asthenia (42% of patients), fever and rashes.
Raltitrexed has been compared with 5FU and leucovorin in patients with previously untreated advanced colorectal cancer.1 After a mean follow-up of 5 months, over half the patients had died or had disease progression. Of the 222 patients given raltitrexed, 44 had a response, compared with 27 of the 212 patients given the other treatment. There were no significant differences in survival or time to progression of the disease. Adverse effects were similar except fewer patients developed thrombocytopenia or mucositis with raltitrexed. However, increases in liver enzymes were more common.
Although the results of treatment with raltitrexed or 5FU and leucovorin are similar, treatment with raltitrexed requires fewer days in hospital. This maybe important to patients with a poor prognosis.
- Tomudex Colorectal Cancer Study Group. 'Tomudex' (ZD 1694):Results of a randomised trial in advanced colorectal cancer demonstrate efficacy and reduced mucositis and leucopenia. Eur J Cancer 1995;31A:1945-54.