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.

Femara (Novartis)
2.5 mg tablets

Indication: breast cancer
Antioestrogens such as tamoxifen are often used in the treatment of advanced breast cancer. In postmenopausal women, including those whose menopause has been induced by treatment, oestriol can be produced by other tissues. This synthesis can be stopped by inhibiting the aromatase enzymes. Anastrozole is already available for postmenopausal women with advanced breast cancers which have progressed following treatment with tamoxifen. Letrozole, another non-steroidal aromatase inhibitor, is now also approved for the same indication.

In a pivotal clinical trial, letrozole was not compared with anastrozole. The comparator was megestrol acetate, a synthetic progestogen. The 551 patients were randomised to receive daily doses of 0.5 mg or 2.5 mg of letrozole or 160 mg megestrol. The overall response rate was 24% in patients given 2.5 mg letrozole. Only 13% of the women given 0.5 mg letrozole and 16% of those given megestrol had a response to treatment. The median time before treatment failed was longest (155 days) in the patients given 2.5 mg letrozole.

Letrozole is taken once a day until the cancer progresses. It is well absorbed and rapidly distributed. The drug is slowly metabolised and then excreted mainly in the urine. As the metabolism may involve cytochrome P450 3A4 and 2A6, there is a potential for interactions with other drugs metabolised by these enzymes. The half-life of letrozole is two days and its concentration takes 2-6 weeks to reach a steady state.

Some of the adverse reactions of letrozole can be predicted by its effects on oestradiol synthesis e.g. hot flushes. The most common adverse effects are headache, nausea and peripheral oedema. In the pivotal study, letrozole was generally better tolerated than megestrol.

Women with breast cancer and their doctors will need to consider carefully the risks and benefits of letrozole. Its efficacy in oestrogen-receptor negative tumours is not yet known. Although letrozole has a higher response rate than megestrol, the median time to progression is not significantly different. When the data from the pivotal trial were collected, there were no statistically significant differences in the risk of death or the median time to death. At that stage, 58% of the women taking letrozole (2.5 mg) and 50% of those taking megestrol were still alive. If further study finds that letrozole has no greater effect on survival than megestrol, patients may still prefer letrozole (or anastrozole) as it is better tolerated.