Q Have you any information on the new breast cancer drug Femara? I have heard that it is better than tamoxifen. – E.P., Glasgow
A Femara is the trade name for a new drug called letrozole, manufactured by Novartis. It got its licence in the USA nearly two years ago as a ‘first-line drug’ for postmenopausal women with breast cancer.
For the last 15 years, tamoxifen, the earlier drug from AstraZeneca, has been the ‘treatment of choice’ for breast cancer. However, when actually put to the test in clinical trials, the drug has been found to be anything but a choice treatment – mainly due to a combination of poor performance and serious side-effects. Recently, a large study on more than 7000 women concluded that ‘the overall risk-to-benefit ratio for the use of tamoxifen in breast cancer prevention is still unclear’ (Lancet, 2002; 360: 817-24).
Now, just when the patent rights on tamoxifen are expiring, along comes a new type of drug called an aromatase inhibitor. Unlike tamoxifen, which is an oestrogen-blocker, the new compound stops the action of aromatase, an enzyme involved in oestrogen production. So, although different, the new drug is basically doing the same thing. Three companies have developed their own versions of it: AstraZeneca’s is called Arimidex, harmacia offers Aromasin and Novartis has Femara.
It’s in the companies’ interests to show that the new compound works better than tamoxifen – and sure enough, clinical trials ‘supported by’ the drug manufacturers have come up with the goods. Arimidex, for example, has been found to be ’17 per cent better’ than tamoxifen; Pharmacia is a bit behind on their Aromasin trials, but three separate studies have already been concluded on Femara.
The largest one to date was done on more than 900 women with breast cancer. They were randomly split into two groups: one that was given 20 mg of tamoxifen; the other took 2.5 mg of Femara per day.
Judging by the headline results, you would think that the world was witnessing a major breakthrough. Femara was reported to be ‘significantly superior’ to tamoxifen, with 30 per cent improvements being quoted.
The small print of the study, however, gives a rather different picture. The major advantage of Femara seems to be that it delays ‘treatment failure’ by less than three months, in other words, it has a marginal effect on arresting the progress of the disease. Furthermore, the doctors admit they found ‘no significant difference . . . in the duration of overall clinical benefit’. They also acknowledge that it is too early to tell whether the new drug will have any effect on actual survival times (J Clin Oncol, 2001; 19: 10).
What about side-effects? Reducing these is often one of the primary aims of a drug company when developing an improved version of an old drug. But if that’s what Novartis was hoping for with Femara, they must be disappointed. Its side-effect profile is almost identical to tamoxifen’s: bone pain, back pain, nausea, joint pain, fatigue and thinning hair are just as frequent with Femara – and those are merely the immediate effects. What the long-term side-effects might be is impossible to assess at present. It took years before tamoxifen was discovered to cause uterine cancer, blood clots and severe gynaecological problems.
One straw in the wind with Femara is thrombophlebitis (vein inflammation with blood clots), a side-effect that is described as ‘common’ even by the manufacturers themselves (Novartis document, July 2001). And blood clots were one of the major causes of death with tamoxifen.
Another straw is that Femara patients are now talking to each other on the Internet and comparing their symptoms. A few are beginning to complain of ‘severe pain below the waist’. One woman finds the pain unbearable, but says forlornly: ‘The doctor makes me feel like if I stop taking the drug, I might as well sign my death warrant.’
Sadly, according to the latest evidence, her doctor is wrong.