A review reporting off-label use of anticancer drugs reports that, between 1990 and 2002, the proportion of off-label drug use in children and adults ranged between 6.7% and 33.2%. The majority of off-label prescription took place within palliative care, concludes the review, which is published in the November edition of The Lancet Oncology.
Off label use of anticancer agents arises because of the increasingly specific labelling applied to drugs when approved by regulatory agencies. For example, panitumumab is approved in the European Union only for pretreated colorectal cancers expressing the ERBB1 receptor and the non-mutated KRAS gene. Use of other drugs can be regarded as off-label if the dose, schedule or route of administration, or duration of treatment is unusual, as well as if the drug is used in an untested combination with another approved anticancer agent.
"Off-label use is most likely to be seen for drugs with narrow indications… that have a broad range of activity," says Dr Levêque. He also notes that although off-label prescription has been reported for most cancer types, the practice is most common "in patients with metastatic or advanced cancer treated with palliative intent". Such patients are not generally expected to experience clinical benefit but there are instances in which off-label anticancer drugs are accepted as the standard of care, such as the use of high-dose carboplatin in some paediatric cancers. The issue of safety then becomes more of a concern, as little information about tolerance or side-effects is likely to be available for the proposed indication.
Dr Levêque also draws attention to the problems of funding off-label anticancer drugs, since oncology is one of the most costly areas of medicine today. The situation varies between countries, but national reimbursement might not be guaranteed for a drug used off-label, particularly in the UK, where decisions on oncology drug reimbursement take account of cost effectiveness.
While applauding the position of drug agencies in Europe and the USA in their move to stimulate clinical research into paediatric studies of off-label oncology products, the review concludes that further studies on the extent of off-label use of anticancer agents are necessary and that accurate and unbiased data is urgently needed to aid decision-making by health professionals.
Dr Dominique Levêque Department of Pharmacy-Pharmacology, Hôpitaux Universitaires de Strasbourg, Hôpital Hautepierre, Avenue Molière, Strasbourg, France dominique.leveque@chru-strasbourg.fr T) +33 (0)3 88 12 82 13
Notes for editors
- A drug is defined as being used off-label if it is used outside the terms of its official labelling, which is created when the drug is approved by a regulatory body such as the FDA in the USA, or EMEA in Europe.
- Studies were identified for inclusion using relevant keywords to scan reports published between 1980 and April 30 2008. Reports in English, French and German were included, but studies on the use of supportive agents or the use of anticancer drugs outside oncology were excluded.
Full Health Care Development paper: http://press.thelancet.com/TLOofflabelfinal.pdf
Journal
The Lancet Oncology