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.
Aromasin (Pharmacia & Upjohn)
25 mg tablets
Approved indication: advanced breast cancer
Australian Medicines Handbook Section 17.10.2
Oestrogen can stimulate the proliferation of breast cancer cells. The main source of oestrogen in postmenopausal women is the conversion of androgens from the adrenal glands. This conversion can be blocked by inhibiting the aromatase enzyme. Exemestane is an aromatase inhibitor. Unlike other aromatase inhibitors, such as aminoglutethimide, anastrozole and letrozole, exemestane has a steroidal structure.
A single dose of exemestane suppresses oestrogen concentrations by 90%. Each dose is well absorbed but the bioavailability is reduced by first-pass metabolism. Patients should take the drug after a meal as this increases plasma concentrations of exemestane by 30-40%. The drug is almost completely metabolised with the metabolites being excreted in the faeces and urine. Clearance is reduced by renal and hepatic impairment.
A double-blind trial has studied exemestane as second-line therapy in postmenopausal women. All the women had breast cancers which had progressed despite treatment with tamoxifen. In this trial 366 women were randomised to take exemestane and 403 took megestrol, a synthetic progestogen with an antitumour action. The objective response rates were 15% for exemestane and 12% for megestrol. This difference is not significant, however exemestane did have some advantages. The median time to progression of the tumour was 20 weeks with exemestane and17 weeks with megestrol. This contributes to a significantly longer median survival time.1
Although there have only been uncontrolled phase II studies, exemestane has also been approved as a third-line treatment. Approximately 9% of women, whose tumours have progressed despite multiple hormone therapies, will respond to exemestane. In women with metastatic disease which had progressed after treatment with a non-steroidal aromatase inhibitor, 7% responded to exemestane.2
Only 3% of the women in the clinical trials had to withdraw because of adverse events. Compared to megestrol, exemestane caused more hot flushes, headaches, rashes, nausea and vomiting.
Exemestane is at least as effective as megestrol, but it has not been compared with other aromatase inhibitors as second-line therapy. As most of the women in the comparative trial1 had hormone-receptor positive tumours, the efficacy of exemestane in oestrogen-receptor negative tumours is uncertain.
- The Exemestane Study Group. Exemestane is superior to megestrolacetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. J Clin Oncol2000;18:1399-411.
- LÃ¸nning PE, Bajetta E, Murray R, Tubiana-Hulin M,Eisenberg PD, Mickiewicz E, et al. Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial. J Clin Oncol 2000;18:2234-44.