Off-label use of anticancer drugs high among patients in palliative care

Review shows that off-label use of anticancer drugs occurs in all types of cancer.

Between 1990 and 2002 the prevalence of the off-label use of anticancer drugs in children and adults in the United States, the United Kingdom, France and Australia ranged from 6.7% to 33.2%, according to review data published in the Lancet Oncology.

The off-label use of these treatments occurs most often in palliative care settings, according to the review author Dominique Levêque, PhD, in the department of pharmacy-pharmacology at the University of Strasbourg in France. He used PubMed to find articles on the off-label use of anticancer drugs published in English, French and German from 1980 to 2008.

Levêque said he was unable to draw definitive conclusions because of a lack of data on the prevalence of the use of anticancer drugs in an off-label fashion. However, after analyzing the available data, he reported that use was most common among children and adults with various types of cancers.

Off-label anticancer drug use

Levêque found that off-label use was reported for most cancer types. A group at his institution reported that hormone-refractory prostate cancer had the highest rate of off-label drug use (58%). Use was also high for bladder cancer (38%) but low for breast cancer (4%). Levêque attributed the increase in off-label use to a lack of approved drugs available at the time of the analysis.

Drugs with narrow indications but a broad range of activity were most likely to be used off-label, according to Levêque. In 2002 he and his colleagues reported that the drugs most frequently used off-label were docetaxel (Taxotere, Sanofi Aventis; 29%), oxaliplatin (Eloxatin, Sanofi Aventis; 24%), fludarabine (8%) and carboplatin (8%).

"Unapproved use is not illegal (at least in western countries). In addition, it may be appropriate. Overall, [unapproved use] can be prevented by limiting funding or by stimulating pharmaceutical companies to extend the indications," Levêque told HemOnc Today.

Some studies on off-label drug use have focused on specific drugs. For example, in the United States from September 1998 to June 2001, one institution reported that 75% of its rituximab (Rituxan, Genentech) administrations were used off-label. According to Levêque, type of cancer was the major category of off-label use (94%).

Improving safety and accepting indications

Responsibility for off-label drug use has been addressed by the European Society for Medical Oncology because of concern that the effects of off-label prescribing fall solely on the physician and pharmacist. The society asked regulatory bodies to take some responsibility, and also proposed the creation of a list of appropriate off-label indications that could potentially be approved by the European Medicines Agency.

"To ensure [patient] safety is to use drugs with the most comprehensive information. For example, to avoid recent agents with unknown or partly known mechanism of action or with insufficient data regarding side effects," Levêque said.

Levêque proposed that reference books, such as the American Hospital Formulary Service’s Drug Information, publish a list of accepted off-label indications. Some in the United States have also proposed creating an independent center for drug information used to track off-label studies and update drug labels to provide timely and accurate data to physicians, according to Levêque. – by Stacey L. Adams

Palliative care physicians are usually not prescribing chemotherapeutic/biologic agents, though we certainly see many patients whose oncologists are prescribing anticancer therapies that are being used for them off-label.

– Stephanie Harman, MD

Director, Inpatient Palliative Care
Stanford Division of General Internal Medicine