The cost of anticancer drugs is always controversial but using the drugs more intelligently and effectively could help to make the budget stretch
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The cost of anticancer drugs is always controversial but using the drugs more intelligently and effectively could help to make the budget stretch
Christine Clark PhD FRPharmS FCPP(Hon)
Editor, HPE
The quest for ‘clinical and cost-effectiveness’ has become a guiding principle of the NHS. Funding for cancer drugs is a frequent headline topic as new and more expensive drugs arrive on the scene every few months. Although there has been much discussion of how to make cancer drugs more affordable, one area that is rarely mentioned is the matter of ensuring that the majority of the dose is absorbed – surely a fundamental pharmaceutical issue when oral dosage forms are used. A number of oral anticancer drugs are poorly absorbed in the fasting state but well-absorbed if taken with food. Nevertheless, they are labelled to be taken fasting, thus ensuring that the majority of the dose is flushed down the toilet. Mark Ratain, a pharmacologist and oncologist from Chicago, has argued the case powerfully (see HPE 72). He did so again as the keynote speaker at HPE LIVE in September.
A prime example is abiraterone. In August, the National Institute for Health and Care Excellence proposed to reject abiraterone for patients with metastatic, hormone-relapsed prostate cancer not previously treated with chemotherapy because, at a cost per QALY of nearly £47,000, it was not cost-effective. The calculation is based on a dose of abiraterone of 1000mg per day, costing £3000 per month. The label stipulates that abiraterone be taken on an empty stomach, although the bioavailability in this circumstance is only 5–10%.
The simple expedient of taking abiraterone with a meal can increase its absorption by five- to tenfold. Indeed, a study is now underway to compare the effects of the standard 1000mg dose, taken fasting, with a 250mg dose taken with food. If this is effective – and there seems no reason why it should not be – then the cost of the drug would fall to £750.00 per month and the cost per QALY would fall dramatically.
Why is this not done anyway? Because this would amount to off-label prescribing with all the associated liability issues. The drug is labelled to be taken fasting to reflect the way it was given in trials. The implied assumption here is that it is better to achieve reliable, low absorption rates than high rates of absorption that might be more variable. Although, as Ratain has noted, there is considerable variability in absorption even when the drug is taken fasting. However, this strategy is not without risk – inadvertent ingestion of food during the critical interval could lead to greater absorption of the drug with the risk of unwanted effects. But why pay for about 90% of the dose to go down the toilet? This really does not pass the common-sense test.
A quick trawl round the internet shows that patients – especially those who have to pay for their medicines – are very much aware of the issues. Some have independently reduced their doses of abiraterone and started taking them with food.
What seems to have happened here is a demonstration of the law of unintended consequences. What is now needed is a new approach to the licensing of oral anticancer drugs to take account of the effects of food on bioavailability. We must hope that the current randomised trial (of low-dose abiraterone with food vs labelled dose) will be the first of many.
Drug absorption and bioavailability are bread and butter to pharmacists, and effective use of oral anticancer agents is a cause that deserves our enthusiastic support both in the interests of safeguarding patients’ welfare and the quest for ‘clinical and cost-effectiveness’.
