Most doctors who write a prescription for therapy for a patient assume that compliance with the prescription will be followed. Unfortunately, this is not always the case. One of the skills of medical practise is to gain the patient’s trust and to figure out when a patient is telling the truth. This is not meant to impugn the patient’s veracity but merely to understand that patients may have many reasons for disguising the facts, which include fear, poor memory, confusion, toxicity and other factors such as embarrassment or a wish to please the doctor.
Toxicity has for many years been underplayed by doctors. It has traditionally been classified as an assessment of serious toxicity in animal studies prior to clinical usage. Although these studies are very important to avoid serious toxicity, they usually fail to address the issue of patient compliance although; to be fair, this is not the end-point of these studies.
A number of studies draw a difference between patient compliance and patient adherence. This may be academically important and relevant in pre-clinical studies but for most patients and doctors the real question is whether a patient is taking their medications, as prescribed, or not.
As a haematologist, one of the most important developments in my lifetime was the development of the drug Imatinib. I was involved in treating leukaemia and carried out the first allogeneic BMT in Ireland. The development of Imatinib was a major breakthrough in the treatment of Chronic Myeloid Leukaemia (CML)
The administration of oral chemotherapy (tyrosine kinase inhibitor) abrogated the Philadelphia chromosome with minimal toxicity, was seen as a major breakthrough by haematologists. However, an unforeseen problem was compliance among patients. Imatinib is often associated with mild diarrhoea which, to physicians, seems a small price to pay with a life-saving drug. However, as a patient once said to me, “mild daily diarrhoea for years becomes a problem”. A problem for some patients too is that daily consumption of Imatinib reminds patients that they have a malignant disease, even if they are relatively asymptomatic.
A number of physicians have tried to address the problem of lack of compliance. François Mahon and David Marin, for example, found that measuring plasma levels of the drug would be a guide as to whether the patient was compliant or not. Usually, higher levels of the drug are associated with a better clinical response so, when present, compliance was assumed. However, it transpired that a number of patients increased their intake of the drug a few days before the measurement was to be carried out.
It may seem difficult to understand why patients should avoid taking oral medication, which is relatively well tolerated and very effective. The situation is complex. Although patients are initially delighted to hear that their malignant disease can be treated with oral therapy, the sense of delight and relief may soon be dissipated. As a haematologist and someone who is taking a Tyrosine Kinase Inhibitor on a daily basis let me try to explain my own experience. Although relatively asymptomatic, the taking of a daily anti-cancer treatment is a stark reminder of one’s mortality. While it may appear to be ungrateful for such treatment, living with the ‘Sword of Damocles’ dangling over one’s head may be difficult psychologically for some patients.
The question on many patient’s lips and is shared with most of their physicians is: can Imatinib be safely discontinued? Recent data, again from Mahon and his group, suggest that Imatinib can be safely discontinued in patients who have had a complete molecular response for two years. They also suggest the possibility that some patients may be cured of Chronic Myeloid Leukaemia after initial successful treatment with a tyrosine kinase inhibitor. However, clearly further follow up is required in larger groups of patients in which their experiences are recorded. Indeed, other questions may come to the surface which have hitherto not been considered.
As we know the human condition is very complex. So, while there is no doubt that huge gains have been made in the treatment of malignancies, the complexities of managing long-term cancer survivors requires far more consideration from haematologists.
About the Author
Shaun Richard McCann received his M.B. from University College Dublin. He became a Member of The Royal College of Physicians in Ireland (MRCPI), by examination, in 1973. He was a specialist medical fellow at the University of Minnesota from 1974-76. The main focus of his research then was red cell structure and function, especially in hereditary spherocytosis. Click here to learn more.