Non-Compliance with Oral Chemotherapy May Be a Cause of Late Relapse in Childhood Leukemia

Reports from the united states have suggested that 10-30% of children with leukemia and other malignancies may not take the oral chemotherapy medications that have been prescribed.1 Studies indicate that urinary excretion of chemotherapy metabolites is greater in supervised inpatients, as opposed to non-supervised outpatients, who have been prescribed the same dose of drug.2 Sub-optimal doses of chemotherapeutic drugs may contribute to late relapse. There is considerable circumstantial evidence that non-compliance with medication may be the basis of the widely different outcomes of acute lymphoblastic leukemia (ALL) seen in different communities and countries, where remission rates are comparable but ultimate survival rates vary markedly. This is true even though treatment protocols are similar.

Lillyman and Lennard, writing from London and Sheffield, argue that if patient non-compliance could be eliminated, many unexpected and unexplained late relapses of standard risk ALL could be prevented, and that the usual 75% survival rate could be increased by as much as 10%. In Britain, this would avoid late relapse in 30-40 children per year.3 In the United States, the number would be much larger.

Non-compliance with medications is a familiar phenomenon in pediatrics. The frequent failure of patients to complete a prescribed 10-day course of oral penicillin for group B streptococcal pharyngitis is well known to all of us. One might intuitively think that medication compliance would be much better when treating more serious diseases. This is not necessarily so, and high rates of non-compliance with medications have been reported in children with asthma, tuberculosis, sickle cell disease, and others.4-6 A serious, and possibly fatal, disease like ALL does not ensure that all children with leukemia will reliably take pills every day for two years, especially when, during most of this time, they feel and appear perfectly well.

Lillyman and Lennard do not have an answer to non-compliance in ALL. It is obviously impractical to give all drugs parenterally or under direct medical supervision. They do suggest that parents and children should be educated, and repetitively reeducated, about the importance of taking oral medications and warned of possible consequences if they do not. They also suggest monitoring compliance by performing frequent and conspicuous measurements of drug metabolite concentration.3—hap

References

1. Tebbi CK. Treatment compliance in childhood and adolescence. Cancer 1993;71:3441-3449.

2. Smith SD, et al. A reliable method for evaluating drug compliance in children with cancer. Cancer 1979;43:169-173.

3. Lilleyman JS, Lennard L. Non-compliance with oral chemotherapy in childhood leukemia: An overlooked and costly cause of late relapse. BMJ 1996;313:1219-1220.

4. Gibson NA, et al. Compliance with inhaled asthma medication in pre-school children. Thorax 1995;50:1274-1279.

5. Byers N, et al. Delay in the diagnosis, notification, and initiation of treatment and compliance in children with tuberculosis. Tuber Lung Dis 1994;75:260-265.

6. Cummins D, et al. Penicillin prophylaxis in children with sickle cell disease in Brent. BMJ 1991;302:989-990.