European Journal of Cancer

Issue 4, 2008

PODIUM – Keep taking the tablets! – with Dr. Ron Mathijssen

Dr Ron Mathijssen (Erasmus Medical Center, Rotterdam, the Netherlands) is completing his oncology training, having previously studied the pharmacokinetics and pharmacogenetics of irinotecan for his PhD. He is the corresponding author of an EJC paper, ‘Lifestyle habits as a contributor to anti-cancer treatment failure’ (Eur J Cancer 2008 44 (3):374-382), which discussed – among other subjects – patients’ non-adherence to anti-cancer treatment regimens.

What do you mean by non-adherence?

Adherence is the extent to which a patient’s behaviour corresponds to that agreed with the healthcare professional. Non-adherence can mean that the patient is not taking the prescribed medicine but it can also mean that they are taking alternative or complementary medicines alongside it, or are ignoring other parts of advice from the healthcare provider. The definition is wide and it is difficult to say at what point the patient is not adhering.

It has been traditionally assumed that non-adherence was not a problem with cancer treatments. Was this a false assumption?

The problem may be more widespread in other medical specialties, but it is serious in oncology. Adherence rates vary between 20% and 100%. The drugs we use have a narrow therapeutic range and are only active if they are given at the recommended dose. If a patient on an oral anti-cancer drug takes only half the dose recommended, we know it will not work. In other areas of medicine – such as statins for high cholesterol levels – it is probably less serious if people take less of their medicine.

Is non-adherence an increasing problem?

Probably. Patients’ attitudes to doctors are changing, they are more likely to question the advice they receive and this probably leads to more non-adherence. We are also increasingly using oral drugs. Intravenous therapies are given in hospital and we know that the correct dose has been given. Sometimes when patients are at home, they take much less of the drugs.

Is it a problem in the evaluation of drugs?

New (oral) drugs are being studied in phase I-IV trials. Patients in trials are probably more compliant than those taking medicines in a regular home setting. That’s only an assumption but patients in clinical trials are followed up more closely and have better social support from the pharmacist and the family doctor during the study period than would be usual afterwards, once the drug has been registered.

Why don’t patients adhere to advice?

It may be an active decision, or carelessness. Some believe that they are better able (than the doctor) to listen to their body and won’t take pills if they don’t feel like it; if they are nauseous, for example. But non-adherence also occurs when patients don’t understand a complex regimen, with too many pills each day. Difficult schemes may lead to patients taking more or less than is required.

Is it a hidden problem?

Patients may believe that it has nothing to do with the doctor, that it’s their decision whether or not to be treated. Patients may also feel ashamed that they aren’t taking pills and be reluctant to admit it. Age, attitude, ethnicity and socio-economic class all play a role. Adolescents for example tend not to adhere because they are in a phase of life where they don’t want to follow strict rules.

Does educational level make a difference?

Yes, in that it is easier to explain to an educated person what the disease involves and why it’s necessary to take pills, especially in the adjuvant setting. But educated people tend to take alternative medicines and do not adhere in that way. They make up their own rules for becoming healthy which may put them in danger of non-adherence.

How widespread is non-adherence?

One study found that patients taking adjuvant tamoxifen were only 50% adherent in the 4th year of therapy (J Clin Oncol 2003; 21: 602-6). We need to recognise this as a major problem. Use of alternative medicines can be dangerous. We found that patients on irinotecan who were also taking St John’s Wort had a 42% reduction in levels of the active drug. That’s an enormous drop. We shouldn’t assume that patients are adherent. If a drug isn’t working, we should consider non-adherence as a possible explanation.

How should clinicians approach the subject?

Asking patients if pill-taking is difficult, or about their expectations of therapy, may reveal non-adherence. A direct question - do you take your pills in the right way? - will seem confrontational. But the subject needs to be explored with patients; every one could be non-adherent in future. This problem is set to get worse as we use more oral drugs, as patients have shorter periods in hospital and less involvement with oncologists. Clinicians need to be aware of the possibility and look out for it. Most cases of non-adherence are not recognised.